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Intercellular Adhesion (intercellular + adhesion)
Kinds of Intercellular Adhesion Terms modified by Intercellular Adhesion Selected AbstractsImmunohistochemical characterization of glomerular inflammatory cells and expression of adhesion molecules in anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclassesPATHOLOGY INTERNATIONAL, Issue 2 2006Tadashi Kado According to previous report, adhesion of CD8-positive cells and macrophages to glomerular endotherial cells through the lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway is crucial for the initiation and subsequent progression of anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY rats. In the present study glomerular inflammatory cell infiltration and LFA-1/ICAM-1 expression were examined in anti-GBM nephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b. The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8-positive cells after administration of IgG2a and IgG2b subclass antibodies was significantly elevated compared to that for the IgG1 subclass. The intensity of glomerular ICAM-1 immunostaining by the IgG2a and IgG2b subclass antibodies tended to be stronger than that by the IgG1 subclass. Glomerular LFA-1-positive cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than that of the IgG1 subclass. These results demonstrate that monoclonal antibodies belonging to the IgG2a and IgG2b subclasses strongly induce glomerular infiltration of inflammatory cells and expression of adhesion molecules in rat anti-GBM nephritis. [source] Endothelial dysfunction in Buerger's disease and its relation to markers of inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006M. Joras Abstract Background, Buerger's disease (BD) is a segmental occlusive vascular disease. The aim of this study was to detect functional changes in brachial artery and asymptomatic morphological changes in extra-cranial carotid arteries not affected by the disease process and to assess markers of inflammation and endothelial damage. Materials and methods, Fourteen patients in the remission phase of BD and the same number of age- and sex-matched healthy controls were included in the study. The capability of endothelium-dependent (flow-mediated) and endothelium-independent dilation of the brachial artery and intima-media thickness of the carotid arteries were measured using high-resolution ultrasound. Laboratory parameters of endogenous fibrinolytic activity, inflammation and endothelial dysfunction were also measured. Results, Patients with BD had a diminished capability of endothelium-dependent vasodilation and higher levels of some circulating markers of inflammation, such as leukocytes, C-reactive protein, intercellular adhesion molecule-1 and E-selectin. Intercellular adhesion molecule-1 levels were related to some of the inflammatory markers (sedimentation rate, C-reactive protein, ,2-globulins and fibrinogen), while E-selectin was correlated with decreased endogenous blood fibrinolytic activity. Endothelium-dependent vasodilation was in negative correlation with the relative share of neutrophil granulocytes. There were no significant differences in intima-media thickness between patients with BD and controls. Conclusions, Our study has expressed generalized functional arterial disorder in patients with BD not accompanied by any measurable morphological changes of the carotid arterial wall. Functional deterioration of brachial artery could be related to increased levels of various inflammatory markers , the process which is most probably the basic pathogenetic mechanism of the disease. [source] Systemic and local effects of long-term exposure to alkaline drinking water in ratsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2001Marina E.T. Merne Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined. [source] Intercellular adhesion molecule-1 gene polymorphisms in Behçet's diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2000D. H. Verity Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases, including multiple sclerosis and inflammatory bowel disease. The expression of both soluble and tissue ICAM-1 is increased in Behçet's disease (BD) but the contribution of ICAM-1 gene polymorphisms to this disease remains unknown. Associations with BD have been reported for genes within the MHC, including HLA-B51, TNF and MICA, but the role of non-MHC genes in BD remains largely unexplored. We have investigated the frequency of the R/G 241 and K/E 469 ICAM-1 gene polymorphisms in 83 patients with BD disease and 103 healthy controls, all of Palestinian and Jordanian descent, and demonstrated an association between BD and the ICAM-1 E469 allele (Pc = 0.046, OR = 2.1). Among patients, no association was found between the presence of ocular disease and ICAM-1 polymorphisms. While the functional correlate of this polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain, which is independent of the MHC, may contribute to disease. [source] Intercellular adhesion and cell separation in plantsPLANT CELL & ENVIRONMENT, Issue 7 2003M. C. JARVIS ABSTRACT Adhesion between plant cells is a fundamental feature of plant growth and development, and an essential part of the strategy by which growing plants achieve mechanical strength. Turgor pressure provides non-woody plant tissues with mechanical rigidity and the driving force for growth, but at the same time it generates large forces tending to separate cells. These are resisted by reinforcing zones located precisely at the points of maximum stress. In dicots the reinforcing zones are occupied by networks of specific pectic polymers. The mechanisms by which these networks cohere vary and are not fully understood. In the Poaceae their place is taken by phenolic cross-linking of arabinoxylans. Whatever the reinforcing polymers, a targeting mechanism is necessary to ensure that they become immobilized at the appropriate location, and there are secretory mutants that appear to have defects in this mechanism and hence are defective in cell adhesion. At the outer surface of most plant parts, the tendency of cells to cohere is blocked, apparently by the cuticle. Mutants with lesions in the biosynthesis of cuticular lipids show aberrant surface adhesion and other developmental abnormalities. When plant cells separate, the polymer networks that join them are locally dismantled with surgical precision. This occurs during the development of intercellular spaces; during the abscission of leaves and floral organs; during the release of seeds and pollen; during differentiation of root cap cells; and during fruit ripening. Each of these cell separation processes has its own distinctive features. Cell separation can also be induced during cooking or processing of fruit and vegetables, and the degree to which it occurs is a significant quality characteristic in potatoes, pulses, tomatoes, apples and other fruit. Control over these technological characteristics will be facilitated by understanding the role of cell adhesion and separation in the life of plants. [source] Intercellular adhesion molecule-1 (ICAM-1) in ulcerative colitis: presence, visualization, and significanceAPMIS, Issue 2010Ben VAINER First page of article [source] Hypoxia attenuates effector,target cell interaction in the airway and pulmonary vascular compartmentCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007S. Meyer Summary Leucocyte infiltration is known to play an important role in hypoxia-induced tissue damage. However, little information is available about hypoxia and interaction of effector (neutrophils) with target cells (alveolar epithelial cells, AEC; rat pulmonary artery endothelial cells, RPAEC). The goal of this study was to elucidate hypoxia-induced changes of effector,target cell interaction. AEC and RPAEC were exposed to 5% oxygen for 2,6 h. Intercellular adhesion molecule-1 (ICAM-1) expression was determined and cell adherence as well as cytotoxicity assays were performed. Nitric oxide and heat shock protein 70 (HSP70) production was assessed in target cells. Under hypoxic conditions enhanced ICAM-1 production was found in both cell types. This resulted in an increase of adherent neutrophils to AEC and RPAEC. The death rate of hypoxia-exposed target cells decreased significantly in comparison to control cells. Nitric oxide (NO) concentration was enhanced, as was production of HSP70 in AEC. Blocking NO production in target cells resulted in increased cytotoxicity in AEC and RPAEC. This study shows for the first time that target cells are more resistant to effector cells under hypoxia, suggesting hypoxia-induced cell protection. An underlying mechanism for this phenomenon might be the protective effect of increased levels of NO in target cells. [source] Tissue surface tensions guide in vitro self-assembly of rodent pancreatic islet cellsDEVELOPMENTAL DYNAMICS, Issue 8 2007Dongxuan Jia Abstract The organization of endocrine cells in pancreatic islets is established through a series of morphogenetic events involving cell sorting, migration, and re-aggregation processes for which intercellular adhesion is thought to play a central role. In animals, these morphogenetic events result in an islet topology in which insulin-secreting cells form the core, while glucagon, somatostatin, and pancreatic polypeptide-secreting cells segregate to the periphery. Isolated pancreatic islet cells self-assemble in vitro into pseudoislets with the same cell type organization as native islets. It is widely held that differential adhesion between cells of the pancreatic islets generates this specific topology. However, this differential adhesion has never been rigorously quantified. In this manuscript, we use tissue surface tensiometry to measure the cohesivity of spherical aggregates from three immortalized mouse pancreatic islet cell lines. We show that, as predicted by the differential adhesion hypothesis, aggregates of the internally segregating INS-1 and MIN6 beta-cell lines are substantially more cohesive than those of the externally segregating ,-TC line. Furthermore, we show that forced overexpression of P-cadherin by ,-TC cells significantly perturbs the sorting process. Collectively, the data indicate that differential adhesion can drive the in vitro organization of immortalized rodent pancreatic islet cells. Developmental Dynamics 236:2039,2049, 2007. © 2007 Wiley-Liss, Inc. [source] Effect of raisin consumption on oxidative stress and inflammation in obesityDIABETES OBESITY & METABOLISM, Issue 11 2008J. W. Rankin Aim:, Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. Methods:, Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F2, (8-epi PGF2,) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. Results:, Urinary 8-epi PGF2, decreased (,22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. Conclusions:, Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress. [source] Higher carotid-radial pulse wave velocity in healthy offspring of patients with Type 2 diabetesDIABETIC MEDICINE, Issue 3 2004O. D. McEleavy Abstract Aims, To determine whether carotid-radial pulse wave velocity (crPWV), a simple non-invasive measurement of muscular artery structure and function, is increased in offspring of patients with Type 2 diabetes compared with well-matched controls with no family history of diabetes. Serum levels of intercellular adhesion molecule-1 (sICAM-1) were also examined. Methods, Offspring (n = 19, M = 8) were recruited via contact with patients attending clinics. Controls (n = 19, M = 8) were recruited by advertisement. crPWV was measured using COMPLIOR. Blood pressure and heart rate were determined and fasting blood taken for measurement of metabolic and endothelial parameters. Results, Offspring and controls were well matched [mean (sd)] for age [33.1 (9.6) vs. 32.8 (9.5) years], body mass index [24.8 (4.9) vs. 24.3 (3.4) kg/m2], waist circumference [78.3 (2.3) vs. 76.3 (2.5) cm], and systolic blood pressure [120 (9.3) vs. 119 (14.2) mmHg]. crPWV was 10% higher in the offspring [9.94 (1.3) m/s] compared with controls [9.01 (1.2) m/s, P = 0.02] despite similar pulse pressure [52 (10.5) vs. 53.5 (9.3) mmHg] and resting heart rate [71 (8.7) vs. 69 (14.0) beats/min]. They also showed a trend toward higher sICAM-1 [217 (55) vs. 188 (40) ng/ml, P = 0.07] concentrations which were also strongly correlated to crPWV in offspring (r = 0.63, P = 0.004). Conclusions, Vascular dysfunction in the form of increased muscular artery stiffness is present from an early stage in subjects at higher risk of developing diabetes. This may be secondary to impaired activation of endothelial signalling pathways in the context of inherited insulin resistance. [source] n-3 polyunsaturated fatty acid supplementation, monocyte adhesion molecule expression and pro-inflammatory mediators in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 1 2001M. J. Sampson SUMMARY Aims To examine the effect of n-3 polyunsaturated fatty acid supplements on the monocyte surface expression of adhesion molecules involved in pro-atherogenic monocyte,endothelial interactions, and on pro-inflammatory mediators in Type 2 diabetes mellitus. Methods Twenty-nine subjects with Type 2 diabetes and 21 controls without diabetes were studied. Monocyte expression of leucocyte function-associated antigens 1 and 3, intercellular adhesion molecule-1, and the major histocompatibility complex class II molecule HLA-DR were measured using a laser flow cytometric method. Supplementation with 2.08 g n-3 fatty acids for 21 days was undertaken and measurements repeated. Plasma soluble adhesion molecule concentrations, plasminogen activator inhibitor-1 activity and antigen and pro-inflammatory mediators (cysteinyl leukotriene and monocyte leukotriene B4) were also measured. Results Groups did not differ in monocyte expression of adhesion molecules or HLA-DR, or in leukotriene production although plasma soluble adhesion molecule concentrations were higher in the diabetes groups (P < 0.05). n-3 fatty acid supplementation influenced neither the expression of these molecules nor plasma soluble adhesion molecule concentrations or leukotriene production. Conclusions This study does not support increased monocyte adhesion molecule expression or abnormal monocyte production of pro-inflammatory mediators as mechanisms for increased atherogenic risk in Type 2 diabetes. Cardioprotective actions of n-3 fatty acids may not be mediated through these mechanisms. [source] Adenosine downregulates cytokine-induced expression of intercellular adhesion molecule-1 on rheumatoid synovial fibroblasts independently of adenosine receptor signalingDRUG DEVELOPMENT RESEARCH, Issue 4 2003Takashi Nakazawa Abstract Adhesion of fibroblast-like synoviocytes (FLSs) to T cells through the interaction of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). We therefore used flow cytometry and quantitative polymerase chain reaction (PCR) to examine the effect of adenosine and its derivatives on expression of ICAM-1 induced by tumor necrosis factor-alpha and interferon-gamma in primary rheumatoid FLSs (RA-FLSs) and E11 cells, an RA-FLS line. Exposing cells to adenosine (5,500 µM) for 24 h in the presence of coformycin, an adenosine deaminase inhibitor, concentration-dependently inhibited cytokine-induced transcription of ICAM-1 mRNA, as well as subsequent surface expression of the protein. Although transcription of all four adenosine receptor isoforms has been detected in FLSs, neither the A1 receptor agonist R-PIA, the A2A receptor agonist CGS21680 nor the A3 agonist Cl-IB-MECA had any effect on cytokine-induced ICAM-1 expression. Conversely, A1/A2 receptor antagonist xanthine amine congener and A2A antagonist ZM240385 both failed to suppress the effect of adenosine. Adenosine appears to inhibit cytokine-induced ICAM-1 expression in FLSs independently of adenosine receptor-mediated signaling. By contrast, the effect of adenosine was neutralized by nitrobenzylmercaptopurin, a nucleoside transporter inhibitor, or by ABT702, an adenosine kinase inhibitor. This suggests that adenosine taken up via the nucleoside transporter is phosphorylated by adenosine kinase, and the resultant phospho-adenosine interferes with the ICAM-1 transcription and cell surface expression. Downregulation of T cell,FLS interaction by adenosine may thus represent a novel approach to the treatment of RA. Drug Dev. Res. 58:368,376, 2003. © 2003 Wiley-Liss, Inc. [source] Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2006A. E. R. Kartikasari Abstract Background, Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation. Materials and methods, Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells. Results, An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections. Conclusions, Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis. [source] Endothelial dysfunction in Buerger's disease and its relation to markers of inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006M. Joras Abstract Background, Buerger's disease (BD) is a segmental occlusive vascular disease. The aim of this study was to detect functional changes in brachial artery and asymptomatic morphological changes in extra-cranial carotid arteries not affected by the disease process and to assess markers of inflammation and endothelial damage. Materials and methods, Fourteen patients in the remission phase of BD and the same number of age- and sex-matched healthy controls were included in the study. The capability of endothelium-dependent (flow-mediated) and endothelium-independent dilation of the brachial artery and intima-media thickness of the carotid arteries were measured using high-resolution ultrasound. Laboratory parameters of endogenous fibrinolytic activity, inflammation and endothelial dysfunction were also measured. Results, Patients with BD had a diminished capability of endothelium-dependent vasodilation and higher levels of some circulating markers of inflammation, such as leukocytes, C-reactive protein, intercellular adhesion molecule-1 and E-selectin. Intercellular adhesion molecule-1 levels were related to some of the inflammatory markers (sedimentation rate, C-reactive protein, ,2-globulins and fibrinogen), while E-selectin was correlated with decreased endogenous blood fibrinolytic activity. Endothelium-dependent vasodilation was in negative correlation with the relative share of neutrophil granulocytes. There were no significant differences in intima-media thickness between patients with BD and controls. Conclusions, Our study has expressed generalized functional arterial disorder in patients with BD not accompanied by any measurable morphological changes of the carotid arterial wall. Functional deterioration of brachial artery could be related to increased levels of various inflammatory markers , the process which is most probably the basic pathogenetic mechanism of the disease. [source] Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2002A. Becker Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng mL,1, respectively). After adjustment for age, gender and glucose tolerance status, subjects with sICAM-1 levels in the upper quartile (,550 ng mL,1) had a relative risk of cardiovascular mortality of 2·05 (95% confidence interval, 1·10,3·81) compared to subjects with sICAM-1 levels in the other quartiles. Further adjustment for classical cardiovascular risk factors or indicators of (sub)clinical atherosclerosis, endothelial dysfunction, inflammation and renal function did not materially alter this relative risk. A high sICAM-1 level was more frequent in subjects with type 2 diabetes than in subjects with a normal glucose tolerance (33·3 vs. 17·8%). Individuals with a plasma concentration of sICAM-1 higher than 550 ng mL,1 had a cardiovascular mortality risk that was twice that of individuals with a lower concentration. Classical cardiovascular risk factors (sub)clinical atherosclerosis, endothelial dysfunction and inflammation do not explain this excess risk. [source] Structural myocardial changes after coronary artery surgeryEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2000F. Eberhardt Background Postoperative contractile dysfunction or ,myocardial stunning' has been described after coronary artery bypass grafting (CABG). In the present study we sought to determine if and to what extent clinical, structural and histochemical evidence of myocardial changes associated with stunning could be found in patients after CABG and cold crystalloid cardioplegia. Materials and methods Left ventricular (LV) biopsies were obtained from CABG patients (n = 10) prior to and at the end of cardiopulmonary bypass (CPB). These biopsies were immunostained for the inducible heat-shock protein 70 (HSP-70i), intercellular adhesion molecule-1 (ICAM-1) and actin. ATP was measured by bioluminescence. Results Biopsies pre-CPB showed no evidence of myocardial damage as HSP-70i was absent and a regular actin cross-striation pattern and only constitutive ICAM-1-expression were present. After CPB we found significantly increased HSP-70i and ICAM-1 levels as well as a deranged actin cross-striation pattern with a widening of actin bands. ATP levels declined from 10 mmol L,1 pre-CPB to 4.9 mmol L,1 after CPB. Correspondingly, coronary sinus effluent showed a significant lactate production. Although, cardiac function determined by transoesophageal echocardiography did not deteriorate, significant inotropic support was necessary to maintain cardiac output. Conclusions Our results present clinical and structural evidence of ,myocardial stunning' after CABG and cold crystalloid cardioplegia. Increased HSP-70i and ICAM-1 expression, as well as a deranged actin cross-striation pattern, might be structural markers to determine ,myocardial stunning' in clinical settings. [source] Astrocytic factors protect neuronal integrity and reduce microglial activation in an in vitro model of N -methyl- d -aspartate-induced excitotoxic injury in organotypic hippocampal slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Nils P. Hailer Abstract Acute CNS lesions lead to neuronal injury and a parallel glial activation that is accompanied by the release of neurotoxic substances. The extent of the original neuronal damage can therefore be potentiated in a process called secondary damage. As astrocytes are known to secrete immunomodulatory and neuroprotective substances, we investigated whether astrocytic factors can attenuate the amount of neuronal injury as well as the degree of microglial activation in a model of excitotoxic neurodegeneration. Treatment of organotypic hippocampal slice cultures with N-methyl- d -aspartate (NMDA) resulted in a reproducible loss of viable granule cells, partial destruction of the regular hippocampal cytoarchitecture and a concomitant accumulation of amoeboid microglial cells at sites of neuronal damage. Astrocyte-conditioned media reduced the amount of NMDA-induced neuronal injury by 45.3%, diminished the degree of microglial activation and resulted in an improved preservation of the hippocampal cytoarchitecture. Transforming growth factor (TGF)-, failed to act as a neuroprotectant and even enhanced the amount of neuronal injury by 52.5%. Direct effects of astrocytic factors on isolated microglial cells consisted of increased microglial ramification and down-regulated expression of intercellular adhesion molecule-1, whereas incubation with TGF-, had no such effects. In summary, our findings show that hitherto unidentified astrocyte-derived factors that are probably not identical with TGF-, can substantially enhance neuronal survival, either by eliciting direct neuroprotective effects or by modulating the microglial response to neuronal injury. [source] Functional estrogen receptors alpha and beta are expressed in normal human salivary gland epithelium and apparently mediate immunomodulatory effectsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2009Maria Tsinti Salivary gland epithelial cells (SGECs) have been shown to participate in immunological responses and have been implicated in the pathogenesis of Sjögren's syndrome (SS). Experimental evidence from animal models indicates that estrogen deficiency may also participate in SS pathogenesis. However, the expression and functionality of the estrogen receptors alpha (ER,) and beta (ER,) in normal human salivary epithelium is unknown. To investigate these points, formalin-fixed, paraffin-embedded specimens and cultured non-neoplastic SGEC lines derived from nine minor salivary gland (MSG) biopsies with normal histology were studied. Immunohistochemical analyses detected the epithelial expression of ER,, ER,1, and ER,2 protein isoforms both in MSG tissues and in cultured SGECs. Such epithelial expression was verified by immunoblotting of various ER proteins in cellular extracts of cultured SGECs (full-length-ER,, ER,-,3, ER,1-long, ER,1-short, and ER,2-long isoforms). Estrogens did not induce growth or apoptosis in cultured SGECs. However, similarly to other cellular systems, treatment of cultured SGECs with estrogens (17,-estradiol and the ER,- and ER,-selective agonists propylpyrazole-triol and diarylpropiolnitrile, respectively) inhibited the interferon-,-inducible expression of intercellular adhesion molecule-1. This finding corroborated the functionality of ER expressed by SGEC. Our results suggest that salivary epithelium expresses constitutively functional ER, and ER, proteins that apparently mediate immunomodulatory effects. [source] Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgarisEXPERIMENTAL DERMATOLOGY, Issue 6 2007Alain De Bruin Abstract:, We recently reported that the pathogenesis of pemphigus vulgaris (PV), an autoimmune blistering skin disorder, is driven by the accumulation of c-Myc secondary to abrogation of plakoglobin (PG)-mediated transcriptional c-Myc suppression. PG knock-out mouse keratinocytes express high levels of c-Myc and resemble PVIgG-treated wild-type keratinocytes in most respects. However, they fail to accumulate nuclear c-Myc and loose intercellular adhesion in response to PVIgG-treatment like wild-type keratinocytes. This suggested that PG is also required for propagation of the PVIgG-induced events between augmented c-Myc expression and acantholysis. Here, we addressed this possibility by comparing PVIgG-induced changes in the desmosomal organization between wild-type and PG knock-out keratinocytes. We found that either bivalent PVIgG or monovalent PV-Fab (known to trigger blister formation in vivo) disrupt the linear organization of all major desmosomal components along cell borders in wild-type keratinocytes, simultaneously with a reduction in intercellular adhesive strength. In contrast, PV-Fab failed to affect PG knock-out keratinocytes while PVIgG cross-linked their desmosomal cadherins without significantly affecting desmoplakin. These results identify PG as a principle effector of the PVIgG-induced signals downstream of c-Myc that disrupt the desmosomal plaque at the plasma membrane. [source] Antioxidant and anti-inflammatory activities of melanocortin peptidesEXPERIMENTAL DERMATOLOGY, Issue 9 2004J. W. Haycock ,-Melanocyte-stimulating hormone (,-MSH) has previously been identified as a potent anti-inflammatory agent in various tissues including the skin. It operates by binding to the melanocortin-1 receptor (MC-1R) which results in the elevation of cyclic AMP. ,-MSH opposes the action of several proinflammatory cytokines including tumour necrosis factor-, (TNF-,). We have shown that ,-MSH can inhibit TNF-,-stimulated activation of nuclear factor-,B (NF-,B) in human cultured melanocytes, melanoma cells, keratinocytes, fibroblasts, Schwann cells and olfactory ensheathing cells. It also inhibits TNF-,-stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in many of these cells and can inhibit peroxide-stimulated activation of glutathione peroxidase, suggesting an antioxidant role. ,-MSH is also able to stimulate intracellular calcium release in keratinocytes and fibroblasts (which do not readily show detectible cyclic AMP elevation) but only in the presence of PIA (an adenosine agonist). The carboxyl terminal tripeptides KPV/KP-D-V are reported to be the minimal sequences necessary to convey anti-inflammatory potential, but evidence on how they act is not fully known. Stable transfection of Chinese hamster ovary cells with MC-1R suggests that the KPV peptides operate by this receptor, at least by elevating intracellular calcium. Elevation of cyclic AMP by these tripeptides has not been detected in any cell type studied; however, calcium elevation can inhibit TNF-,-stimulated NF-,B activity (as for cyclic AMP). In conclusion, the MSH peptides convey anti-inflammatory and antioxidant activity in many cell types in skin and nerve, by counteracting proinflammatory cytokine signalling. The KPV peptides appear to act functionally via the MC-1R and can also elevate intracellular calcium. [source] Impaired intercellular adhesion and immature adherens junctions in merlin-deficient human primary schwannoma cellsGLIA, Issue 5 2008C. Flaiz Abstract Schwannomas that occur spontaneously or in patients with neurofibromatosis Type 2, lack both alleles for the tumor suppressor and plasma membrane-cytoskeleton linker merlin. We have shown that human primary schwannoma cells display activation of the RhoGTPases Rac1 and Cdc42 which results in highly dynamic and ongoing protrusive activity like ruffling. Ruffling is an initial and temporally limited step in the formation of intercellular contacts like adherens junctions that are based on the cadherin-catenin system. We tested if there is a connection between Rac1-induced ongoing ruffling and the maintenance, stabilization and functionality of adherens junctions and if this is of relevance in human, merlin-deficient schwannoma cells. We show intense ongoing ruffling is not limited to membranes of single human primary schwannoma cells, but occurs also in membranes of contacting cells, even when confluent. Live cell imaging shows that newly formed contacts are released after a short time, suggesting disturbed formation or stabilization of adherens junctions. Morphology, high phospho-tyrosine levels and cortactin staining indicate that adherens junctions are immature in human primary schwannoma cells, whereas they display characteristics of mature adherens junctions in human primary Schwann cells. When merlin is reintroduced, human primary schwannoma cells show only initial ruffling in contacting cells and adherens junctions appear more mature. We therefore propose that ongoing Rac-induced ruffling causes immature adherens junctions and leads to impaired, nonfunctional intercellular adhesion in aggregation assays in merlin-deficient schwannoma cells that could be an explanation for increased proliferation rates due to loss of contact inhibition or tumor development in general. © 2008 Wiley-Liss, Inc. [source] Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosisHEPATOLOGY, Issue 2 2000Nils Kinnman M.D. The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the ,F508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of ,F508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease. [source] Catalposide, a compound isolated from Catalpa Ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in miceINFLAMMATORY BOWEL DISEASES, Issue 5 2004Sang-Wook Kim MD Abstract Certain irinoid-producing plants have been used as herbal anti-inflammatory remedies. Here we evaluated whether catalposide (CATP), a single compound isolated from irinoid-producing plant Catalpa ovata, has a potential for preventing or ameliorating diseases characterized by mucosal inflammation. Preliminary microarray-based gene expression test revealed that CATP, which alone did not significantly affect expression of any of the >8,000 genes analyzed, attenuated the expression of tumor necrosis factor-, (TNF-,)-induced proinflammatory genes including interleukin-8 (IL-8) in human intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal transduction study revealed that CATP significantly attenuates TNF-,-mediated p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further, CATP reduced NF-,B-mediated transcriptional activation as well as I,-B, degradation. To establish the in vivo relevance of these findings, we examined whether CATP could affect intestinal inflammation in vivo using the mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. Intrarectal administration of CATP dramatically reduced the weight loss, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP suppressed the expression of TNF-,, interleukin-1,, and intercellular adhesion molecule-1 along with the inhibition of NF-, B p65 translocation into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP may be an effective agent for the treatment of diseases characterized by mucosal inflammation. [source] Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Alexander Margulis Abstract The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd -Ecad). Three-dimensional human tissue constructs harboring either H-2Kd -Ecad-expressing or control II-4 cells (pBabe, H-2Kd -Ecad,C25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd -Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 ,2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease. © 2005 Wiley-Liss, Inc. [source] Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2003Alan J. Thomas Abstract Background Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Methods We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n,=,20) and control (n,=,20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). Results We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p,=,0.01) and a trend towards an increase for VCAM-1 (p,=,0.10). In the gyral white matter there was a trend towards significance for both molecules (p,=,0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. Conclusions These findings are consistent with white matter ischemia in the DLPFC and lend support to the ,vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future. Copyright © 2002 John Wiley & Sons, Ltd. [source] Association between ICAM-1 Gly-Arg polymorphism and renal parenchymal scarring following childhood urinary tract infectionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2006R. A. Gbadegesin Summary Renal parenchymal scarring (RPS) following urinary tract infection (UTI) is an important cause of renal morbidity in children. Studies have shown that the intensity of the inflammatory response following infection is related to the risk of RPS. However, genetic variability in this response has not been studied. Adhesion molecules play a crucial role in leucocyte recruitment following infection, and polymorphisms have been reported in the genes for key cell adhesion molecules. We have investigated the possibility that children who develop RPS following UTI may exhibit altered genotype or allele frequencies for polymorphisms of the intercellular adhesion molecule-1 (ICAM-1) (exons 4 and 6), E-selectin (exons 2 and 4), platelet endothelial cell adhesion molecule-1 (PECAM-1) (exon 3) and CD11b (3,UTR) genes, which may predict outcome of UTI. DNA was isolated from 99 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI and 170 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis. When the RPS group was compared with the NS group, there was a significant reduction in the frequency of the ICAM-1 exon 4 A allele (10.6 vs. 21.3%, respectively, ,2= 6.01, P= 0.014). There was no significant difference in either allele or genotype frequency for any of the other polymorphisms studied. These data suggest that the A allele of the ICAM-1 exon 4 polymorphism may protect against the risk of RPS following UTI and may participate in the regulation of the inflammatory response following UTI. [source] Distribution and Correlates of Lipoprotein-Associated Phospholipase A2 in an Elderly Cohort: The Cardiovascular Health StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2008Curt D. Furberg MD OBJECTIVES: To determine whether high levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with prevalent cardiovascular disease (CVD) and to evaluate factors most influencing Lp-PLA2 levels in a community-based cohort of older adults. DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS), a population-based cohort study of men and women aged 65 and older. PARTICIPANTS: Five thousand five hundred thirty-one CHS participants. MEASUREMENTS: Levels of Lp-PLA2 activity were determined using stored blood samples from the baseline examination. RESULTS: Mean Lp-PLA2 was higher in participants with electrocardiographically determined ventricular conduction defect and major Q-wave abnormality and was positively correlated with left ventricular (LV) mass. It was high in those with echocardiographically determined abnormal LV ejection fraction, which persisted after adjustment. Mean Lp-PLA2 was also higher in participants with mild renal insufficiency and kidney disease. After multivariable adjustment, there was a modest but significant 27% greater risk of prevalent CHF per standard deviation increment of Lp-PLA2 and a modest but significant 12% greater risk of prevalent myocardial infarction. Lp-PLA2 was weakly but mainly most strongly correlated with cholesterol and lipoproteins, but those correlations were not especially strong. Lp-PLA2 was weakly positively correlated with soluble intercellular adhesion molecule-1 but not interleukin-6. In total, all factors considered could explain only 29% of Lp-PLA2 activity. CONCLUSION: Novel findings in the study are the associations, in those aged 65 and older, between Lp-PLA2 activity and LV dysfunction, CHF, and renal disease. CVD risk factors only minimally explain levels of Lp-PLA2. [source] The expression of E-selectin and chemokines in the cultured human lymphatic endothelium with lipopolysaccharidesJOURNAL OF ANATOMY, Issue 5 2008Yoshihiko Sawa Abstract This study investigated the expression of selectins and chemokines in cultured human lymphatic endothelial cells stimulated with lipopolysaccharides. In microarray, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expressions in the lymphatic endothelium with lipopolysaccharides did not change at 0.5 h but increased two- to three-fold at 12 h, whereas E-selectin increased 10-fold at 0.5 h and 68-fold at 12 h compared with untreated cells. The E-selectin mRNA and protein increased in the lymphatic endothelial cells with lipopolysaccharides at more than two-fold levels compared with human umbilical vein endothelial cells. Induction of Cys-Cys chemokine ligand 2, 3, 5, 7, 8 and 20 mRNAs in the lymphatic endothelial cells with lipopolysaccharides was detected in microarray and real-time PCR. The Cys-Cys chemokine ligand 2, 5 and 20 mRNA amounts in cells with high concentration lipopolysaccharides were larger in the lymphatic endothelial cells than in human umbilical vein endothelial cells. The Cys-Cys chemokine ligand 3 and 8 mRNAs were not detected in human umbilical vein endothelial cells. Induction of Cys-X-Cys chemokine ligand 1, 3, 5, 6 and 8 mRNAs was detected in the lymphatic endothelial cells with lipopolysaccharides. The Cys-X-Cys chemokine ligand 3, 5 and 8 mRNA amounts in cells with high concentration lipopolysaccharides were larger in the lymphatic endothelial cells than in human umbilical vein endothelial cells. In conclusion, it was demonstrated that the cultured human lymphatic endothelial cells express E-selectin and phagocyte-attractive chemokine genes. [source] Dexamethasone inhibits lipopolysaccharide-induced hydrogen sulphide biosynthesis in intact cells and in an animal model of endotoxic shockJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Ling Li Abstract Dexamethasone (1 mg/kg, i.p.) administered either 1 hr before or 1 hr after E. coli lipopolysaccharide (LPS, 4 mg/kg, i.p.) in conscious rats inhibited the subsequent (4 hrs) rise in plasma cytokine (interleukin [IL]-1,, tumour necrosis factor [TNF]-,), nitrate/nitrite (NO×), soluble intercellular adhesion molecule-1 (sICAM-1) concentration and lung/liver myeloperoxidase activity indicative of an anti-inflammatory effect. Dexamethasone also reduced the LPS-evoked rise in plasma hydrogen sulphide (H2S) concentration, liver H2S synthesizing activity and expression of cystathionine , lyase (CSE) and inducible nitric oxide synthase (iNOS). Mifepristone (RU-486) inhibited these effects. Dexamethasone (1,10 ,M) reduced the LPS-evoked release of IL-1,, TNF-, and L-selectin, decreased expression of CSE and iNOS and diminished nuclear factor ,B (NF-,B)-DNA binding in isolated rat neutrophils. In contrast, NaHS (100 ,M) increased L-selectin release from rat neutrophils. Dexamethasone also reduced LPS-induced up-regulation of CSE in foetal liver cells. 6-amino-4-(4-phenoxyphenylethylamino) quinazoline (QNZ, 10 nM), a selective inhibitor of transcription via the NF-,B pathway, abolished LPS-induced up-regulation of CSE expression. We propose that inhibition of CSE expression and reduction in formation of the pro-inflammatory component of H2S activity contributes to the anti-inflammatory effect of dexamethasone in endotoxic shock. Whether H2S plays a part in the anti-inflammatory effect of this steroid in other forms of inflammation such as arthritis or asthma warrants further study. [source] Heparin modulates the growth and adherence and augments the growth-inhibitory action of TNF-, on cultured human keratinocytesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Ilkka T. Harvima Abstract Previous works suggest the involvement of mast cells in the epithelialization of chronic wounds. Since heparin is a major mediator stored in the secretory granules of mast cells, the purpose of this work was to elucidate the function of heparin in epithelialization using in vitro culture models. For this, low- and high-calcium media in monolayer and epithelium cultures of keratinocytes were used. Also, an assay based on keratinocyte adherence onto plastic surface was used as well. Heparin (0.02,200 ,g/ml) inhibited keratinocyte growth in a non-cytotoxic and dose-dependent manner in low- and high-calcium media, Keratinocyte-SFM® and DMEM, in the absence of growth factors and serum. Also, heparin inhibited the growth of keratinocyte epithelium in the presence of 10% fetal calf serum and DMEM. Instead, in the presence of Keratinocyte-SFM and growth factors, heparin at 2 ,g/ml inhibited the growth by 18% but at higher heparin concentrations the inhibition was reversed to baseline. TNF-, is another preformed mediator in mast cell granules and it inhibited keratinocyte growth in monolayer and epithelium cultures. Interestingly, heparin at 2,20 ,g/ml augmented or even potentiated this growth-inhibitory effect of TNF-,. The association of TNF-, with heparin was shown by demonstrating that TNF-, bound tightly to heparin-Sepharose chromatographic material. However, heparin could not augment TNF-,-induced cell cycle arrest at G0/G1 phase or intercellular adhesion molecule-1 expression in keratinocytes. In the cell adherence assay, heparin at 2 ,g/ml inhibited significantly by 12,13% or 33% the adherence of keratinocytes onto the plastic surface coated with fibronectin or collagen, respectively, but this inhibition was reversed back to baseline at 20 or 200 ,g/ml heparin. Also, heparin affected the cell membrane rather than the protein coat on the plastic surface. In conclusion, heparin not only inhibits or modulates keratinocyte growth and adherence but it also binds and potentiates the growth-inhibitory function of TNF-,. © 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||||||||