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Chronic Inflammatory Response (chronic + inflammatory_response)
Selected AbstractsOxidative damage of retinal pigment epithelial cells and age-related macular degenerationDRUG DEVELOPMENT RESEARCH, Issue 5 2007Suofu Qin Abstract Damage to the retinal pigment epithelial (RPE) cells is an early and crucial event in the molecular pathways leading to clinically relevant age-related macular degeneration (AMD) changes. Oxidative stress, the major environmental risk factor for atrophic AMD, causes RPE injury that results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration ultimately leads to a progressive irreversible degeneration of photoreceptors. In vitro studies show that oxidant-treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during the early phase of atrophic AMD. The main target of oxidative injury appears to be mitochondria, an organelle known to accumulate genomic damage during aging. Addition of GSH, the most abundant intracellular thiol antioxidant, protects RPE cells from oxidant-induced apoptosis. Similar protection occurs with dietary enzyme inducers that increase GSH synthesis. In addition, enhancing survival signaling preserves RPE cells under oxidative stress. These results indicate that therapeutic or nutritional intervention to enhance the antioxidant capacity and survival signaling of RPE may provide an effective way to prevent or treat AMD. This review describes major molecular and cellular events leading to RPE death, and presents currently used and new experimental, forthcoming therapeutic strategies. Drug Dev Res 68:213,225, 2007. © 2007 Wiley-Liss, Inc. [source] Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunitiesINFLAMMATORY BOWEL DISEASES, Issue 5 2006Stephen B Hanauer MD Abstract Ulcerative colitis (UC) and Crohn's disease (CD), the primary constituents of inflammatory bowel disease (IBD), are precipitated by a complex interaction of environmental, genetic, and immunoregulatory factors. Higher rates of IBD are seen in northern, industrialized countries, with greater prevalence among Caucasians and Ashkenazic Jews. Racial gaps are closing, indicating that environmental factors may play a role. IBD is multigenic, with the most clearly established genetic link between certain NOD2 variants and CD. Regardless of the underlying genetic predisposition, a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the pathogenesis of IBD, especially CD. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or virus or a defective mucosal barrier. The characteristic inflammatory response begins with an infiltration of neutrophils and macrophages, which then release chemokines and cytokines. These in turn exacerbate the dysfunctional immune response and activate either TH1 or TH2 cells in the gut mucosa, respectively associated with CD and, less conclusively, with UC. Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD. [source] NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2005António Carlos Ferreira BSc Abstract Background:NOD2/CARD15 was described as the first susceptibility gene to Crohn's disease (CD). Polymorphisms in the TNFA gene and in the IL1 gene cluster, which are associated with an enhanced chronic inflammatory response, may also play a role in the development of CD. The aim of this study was to determine the association of polymorphisms in the CARD15, TNFA, IL1B, and IL1RN genes with risk of development of CD and with the clinicopathological profile of CD patients. Methods: In a case-control study including 235 CD patients and 312 controls (929 controls for TNFA genotyping), the CARD15 (R702W, G908R, and1007fs), TNFA (,308G/A and ,857C/T), IL1B (,511C/T), and IL1RN (intron 2 variable number of tandem repeats) polymorphisms were genotyped. Results: We observed a significant association between CD and the CARD15 polymorphisms, with an odds ratio (OR) of 2.9 [95% confidence interval (CI), 1.9 to 4.6] for carriers of 1 variant allele and an OR of 11.8 (95% CI, 3.5 to 40.4) for carriers of 2 variant alleles. Patients with CARD15 polymorphisms had more frequently ileal or ileocolonic disease location, stricturing phenotype, abdominal surgery, and no extraintestinal manifestations. The TNFA -308A/A genotype was associated with susceptibility to CD with an OR of 3.0 (95% CI, 1.2 to 7.2). TNFA -308A/A homozygotes showed a higher frequency of erythema nodosum and arthritis, colonic disease location, and absence of abdominal surgery. No associations were found with the TNFA -857, IL1B -511, and the IL1RN VNTR polymorphisms. Conclusions: These findings suggest that CARD15 and TNFA -308 genetic polymorphisms are associated with increased risk of CD displaying distinct clinicopathological profiles. [source] Fluoropassivation and gelatin sealing of polyester arterial prostheses to skip preclotting and constrain the chronic inflammatory responseJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2010Xingyi Xie Abstract Fluoropassivation and gelatin coating have been applied to polyethylene terephthalate (PET) vascular prosthesis to combine the advantages of both polytetrafluoroethylene (PTFE) and PET materials, and to eliminate the preclotting procedure. The morphological, chemical, physical, and mechanical properties of such prostheses were investigated and compared with its original model. Fluoropassivation introduced OCF3, CF3, and CFCF2 structures onto the surface of the polyester fibers. However, the surface fluorine content was only 28,32% compared to the 66% in expanded PTFE (ePTFE) grafts. The fluoropassivation decreased the hydrophilicity, slightly increased the water permeability, and marginally lowered the melting point and the crystallinity of the PET fibers. After gelatin coating, the fluoropassivated and nonfluoropassivated prostheses showed similar surface morphology and chemistry. While gelatin coating eliminated preclotting, it also renders the prostheses slightly stiffer. The original prosthesis had the highest bursting strength (275 N), with the fluoropassivated and gelatin-sealed devices showing similar bursting strength between 210 and 230 N. Fluoropassivation and gelatin coating lowered the retention strength by 23 and 30% on average, respectively. In vitro enzymatic incubation had only marginal effect on the surface fluorine content of the nongelatin-sealed prostheses. However, the gelatin-sealed ones significantly lost their surface fluorine after in vitro enzymatic incubation (by 69,85%) or in vivo 6-month implantation (by 51,60%), showing the lability of the fluoropolymer layer under the hostile biological environment. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010 [source] Ascochlorin suppresses oxLDL-induced MMP-9 expression by inhibiting the MEK/ERK signaling pathway in human THP-1 macrophagesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Jeong Han Kang Abstract The critical initiating event in atherogenesis involves the invasion of monocytes through the endothelial walls of arteries and the transformation of monocytes from macrophages into foam cells. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) and can then be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). Also, during a chronic inflammatory response, monocytes/macrophages produce the 92-kDa matrix metalloproteinase-9 (MMP-9) that may contribute to the extravasation, migration, and tissue remolding capacities of the phagocytic cells. Here, we investigate the effect of ascochlorin (ASC), a prenylphenol antiviral compound from the fungus Ascochyta viciae, on oxLDL-induced MMP-9 expression and activity in human THP-1 macrophages. ASC reduced oxLDL-induced MMP-9 expression and activity in a time-dependent and dose-dependent manner. Also, an analysis of MMP-9 activity using pharmacologic inhibitors showed that ASC inhibits MMP-9 activity via the extracellular signal-regulated kinase 1 and kinase 2 pathways. Our results suggest that ASC may be useful as a potent clinical antiatherogenic agent, a topic of considerable interest in the biological chemistry of chemotherapeutic agents. J. Cell. Biochem. 102: 506,514, 2007. © 2007 Wiley-Liss, Inc. [source] Inflammatory bowel disease pathogenesis: therapeutic implicationsJOURNAL OF DIGESTIVE DISEASES, Issue 1 2005Claudio FIOCCHI The pathogenesis of inflammatory bowel disease (IBD) is complex, involving environmental, genetic, microbial, and immune factors. Therefore, treatment should target components that either predispose to or mediate the chronic inflammatory response of IBD. At the moment it is assumed that all components are necessary to have the typical manifestations of IBD but, in reality, it is unclear to what extent each factor contributes to the disease process, and whether some are more important than others. In addition, some factors are not practical targets; for example, environmental factors are poorly defined, too numerous, and require changes that cannot be implemented by the physician or the patient alone. The same is true for genetic factors that are still not amenable to therapeutic manipulations for technical and ethical reasons. This leaves microbial and immune factors as the two categories that can be selected for therapeutic intervention and where all current treatments are focused. The commensal gut flora can be qualitatively or quantitatively modified with antibiotics, probiotics, or diet, and a better characterization of enteric bacteria strains should help greatly in developing more effective therapies. Most current drugs are focused on inhibiting pro-inflammatory molecules produced by immune cells, including biological agents that block specific cytokines such as tumor necrosis factor-alpha. It is anticipated that combination therapies targeting multiple pathogenic components will prove more effective than those blocking single components of IBD pathogenesis. [source] Prostaglandin E2 secretion from gingival fibroblasts treated with interleukin-1,: effects of lipid extracts from Porphyromonas gingivalis or calculusJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2001Frank C. Nichols Complex lipids of Porphyromonas gingivalis have been identified in lipid extracts from calculus-contaminated root surfaces and in diseased gingival tissues. However, little is known about the biological effects of these complex lipids on host cells. The purpose of this study was to evaluate the effects of P. gingivalis or calculus lipids on prostaglandin secretion from gingival fibroblasts. Lipids were extracted from paired subgingival plaque and teeth samples, and calculus-contaminated root surfaces before and after scaling and root planing, in order to determine the relevant levels of lipid extracts for the treatment of gingival fibroblasts in culture. Primary cultures of gingival fibroblasts were exposed to lipid extracts from either P. gingivalis or calculus/teeth for a period of 7 days. Control and lipid-treated cultures were exposed to human recombinant interleukin-1, for 48 h and prostaglandin secretion from interleukin-1,-treated fibroblasts was compared with control and lipid-treated fibroblasts without interleukin-1, treatment. These experiments demonstrated that P. gingivalis lipids or calculus-tooth lipids potentiate interleukin-1,-mediated prostaglandin secretory responses from gingival fibroblasts. Additionally, P. gingivalis or calculus-tooth lipid extracts were readily taken up by gingival fibroblasts as measured by bacterial fatty acid recovery in lipid extracts of cultured fibroblasts. These results indicate that bacterial lipid penetration into gingival tissues in combination with a chronic inflammatory response may substantially potentiate prostaglandin secretion from gingival fibroblasts, thereby promoting tissue destructive processes associated with adult periodontitis. [source] Glycosaminoglycans and the peritoneaumNEPHROLOGY, Issue 5 2002Susan YUNG SUMMARY: The introduction of peritoneal dialysis (PD) over two decades ago has allowed us to manipulate the peritoneal membrane to perform as a continuous dialysing organ. to maximize the efficacy of solute transport and waste removal, conventional PD fluids require unphysiological concentrations of glucose to provide the osmotic drive, lactate to alleviate metabolic acidosis, and a low pH to prevent the caramelization of glucose during the preparation of the solutions. These factors either alone or in combination, are irritants to the peritoneal membrane. Thus, continuous exposure of the peritoneum to PD solutions, together with frequent episodes of peritonitis confers a chronic inflammatory response within the peritoneum. It is, therefore, not unexpected that with time, long-term PD patients develop structural and functional changes within the peritoneum, which in many cases develop into peritoneal fibrosis of varying degrees and compromises the peritoneal membrane as a dialysing organ. to date, numerous studies have investigated methods to improve the efficiency of PD and preserve the structure of the peritoneal membrane. Recently, a number of reports have documented the beneficial effects of intraperitoneal administration of glycosaminoglycans (GAGs) on both the structural and functional qualities of the peritoneum. In this context, GAGs have been demonstrated to inhibit collagen synthesis within the peritoneum, decrease peritoneal advanced glycosylated end-products (AGE) deposition, and modulate cytokine and growth factor synthesis. This review will examine the available data with regards to the potential role of GAGs in maintaining ultrafiltration, solute transport and the structural integrity of the peritoneum. [source] Platelet-activating factor and human meningiomasNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2006Y. Denizot Meningiomas are common primary intracranial tumours. Platelet-activating factor (PAF) is an inflammatory and angiogenic lipid mediator involved in several types of cancer. The presence of PAF receptor (PAF-R) transcripts, the levels of PAF, the phospholipase A2 activity (PLA2, the enzymatic activity implicated in PAF formation) and the PAF acetylhydrolase activity (AHA, the PAF degrading enzyme) were investigated in 49 human meningiomas. PAF-R transcripts, PAF, PLA2 and AHA were detected in meningiomas. However, their levels did not correlate with biological parameters such as the tumour grade, the presence of associated oedema, necrosis, mitotic index as well as intensity of the neovascularization and chronic inflammatory response. In conclusion, PAF is present in meningiomas where it might act on tumour growth by altering the local angiogenic and/or cytokine networks as previously suggested for human breast and colorectal cancer. [source] Mature teratoma of the uterine cervix with lymphoid hyperplasiaPATHOLOGY INTERNATIONAL, Issue 5 2003Sung-chul Lim A rare case of an extragonadal teratoma, which occurred primarily in the uterus, is described. The tumor developed in the uterine cervix as a conventional cervical polyp, 3 months after an elective abortion in a 27-year-old woman. Microscopically, the solid 2.2 × 1.8 × 1.5 cm mass was a mature teratoma with exuberant lymphoid elements. It consisted of ectodermal, mesodermal and endodermal derivatives. The lymphoid elements may have been a lymphoid hyperplasia, a chronic inflammatory reaction or a component of the teratoma. However, as the lymphoid tissues had no spatial relation to the teratomatous components, the possibility of a teratomatous element was excluded. This could be regarded as a result of an immunological reaction to the tissues composing the tumor, rather than just a chronic inflammatory response because the lymphoid reaction was present in the tumor, the tumor,host interface and the perivascular areas. Because of the patient's history of an abortion and a lymphoid reaction, the possibility of fetal remnants implantation was raised, so DNA typing to compare the teratoma portion with a normal portion of the host was performed. We found the teratoma portions to be in accordance with that of the host, and hence ruled out fetal remnants implantation. This case showed that a mature teratoma of the uterine cervix may manifest as a feature of implanted fetal tissue. In addition, a real teratoma should be included in the differential diagnosis of uterine teratomatous lesion, even when detected in patients with a recent history of pregnancy and lymphoid hyperplasia. [source] Cytokine Induction in Patients Undergoing Regular Online Hemodiafiltration TreatmentARTIFICIAL ORGANS, Issue 7 2000Lajos Vaslaki Abstract: End-stage renal disease (ESRD) patients are known to suffer from chronic inflammation as the result of an ongoing subacute cytokine induction, which may contribute considerably to dialysis-related, long-term morbidity and mortality. Preparation of infusate from cytokine-inducing dialysis fluid and its administration in large quantities as well as the use of high-flux membranes bear the risk of aggravating the chronic inflammatory response among online hemodiafiltration (online HDF) patients. In order to assess the inflammatory risk associated with online HDF, we compared the cytokine induction profile of ESRD patients receiving either online HDF or low-flux hemodialysis (low-flux HD). Specifically, we measured spontaneous and lipopolysaccharide (LPS)-stimulated tumor necrosis factor , (TNF,) and interleukin-1 receptor antagonist (IL-1Ra) release during ex vivo incubation of whole blood. Ultrapure dialysis fluid and polysulfone membranes were used for both treatment modalities. LPS-stimulated release of TNF, and IL-1Ra was elevated for both online HDF and low-flux HD patients compared to healthy individuals (TNF,: 2,336 ± 346 and 2,192 ± 398 versus 1,218 ± 224 pg/106 white blood cells [WBC]; IL-1Ra: 2,410 ± 284 and 2,326 ± 186 versus 1,678 ± 219 pg/106 WBC). Likewise, spontaneous production of TNF,, but not IL-1Ra, was higher in online HDF and low-flux HD patients than in normal controls (37 ± 32 and 22 ± 19 versus 0.8 ± 0.3 pg TNF,/106 WBC). There was no difference in spontaneous and LPS-stimulated cytokine release between both dialysis groups. In addition, intradialytic cytokine induction was not significant for either treatment modality as spontaneous and LPS-stimulated cytokine release were not increased postdialysis. These findings indicate that online HDF does not contribute to chronic leukocyte activation and, consequently, does not place ESRD patients at greater risk with respect to inflammatory morbidity and mortality. [source] Role of ,4,1 Integrins in Chemokine-Induced Monocyte Arrest under Conditions of Shear StressMICROCIRCULATION, Issue 1 2009SHARON J. HYDUK ABSTRACT Monocyte recruitment or emigration to tissues is an essential component of host defense in both acute and chronic inflammatory responses. Sequential molecular interactions mediate a cascade of tethering, rolling, arrest, stable adhesion, and intravascular crawling that culminates in monocyte diapedesis across the vascular endothelium and migration through the basement membrane of postcapillary venules. Integrins are complex adhesion and signaling molecules. Dynamic alterations in their conformation and distribution on the monocyte cell surface are required for many steps of monocyte emigration. Intracellular signaling initiated by chemokine receptors induces conformational changes in integrins that upregulate their affinity for ligands, and this is essential for monocyte arrest. This review focuses on the activation of monocyte ,4,1 integrins by endothelial chemokines, which is required for the arrest of monocytes rolling on vascular cell adhesion molecule 1 under shear flow. Using soluble ligand-binding assays and adhesion assays in parallel-plate flow chambers, critical signaling mediators in chemokine-induced ,4,1 integrin affinity upregulation and monocyte arrest have been identified, including phospholipase C, calcium, and calmodulin. [source] Effects of oral commensal and pathogenic bacteria on human dendritic cellsMOLECULAR ORAL MICROBIOLOGY, Issue 2 2009T. Chino Background/aims:, The oral cavity harbors a diverse and complex microbial community. Bacteria accumulate on both the hard and soft oral tissues in sessile biofilms and engage the host in an intricate cellular dialog, which normally constrains the bacteria to a state of commensal harmony. Dendritic cells (DCs) are likely to balance tolerance and active immunity to commensal microorganisms as part of chronic inflammatory responses. While the role played by DCs in maintaining intestinal homeostasis has been investigated extensively, relatively little is known about DC responses to oral bacteria. Methods:, In this study, we pulsed human monocyte-derived immature DCs (iDCs) with cell wall extracts from pathogenic and commensal gram-positive or gram-negative oral bacteria. Results:, Although all bacterial extracts tested induced iDCs to mature and produce cytokines/chemokines including interleukin-12p40, tumor necrosis factor-,, and monocyte chemoattractant protein-1 (MCP-1), the most important factor for programming DCs by oral bacteria was whether they were gram-positive or gram-negative, not whether they were commensal or pathogenic. In general, gram-negative oral bacteria, except for periodontopathic Porphyromonas gingivalis, stimulated DC maturation and cytokine production at lower concentrations than gram-positive oral bacteria. The threshold of bacteria needed to stimulate chemokine production was 100-fold to 1000-fold lower than that needed to induce cytokines. In addition, very low doses of oral commensal bacteria triggered monocytes to migrate toward DC-derived MCP-1. Conclusion:, Oral commensal and pathogenic bacteria do not differ qualitatively in how they program DCs. DC-derived MCP-1 induced in response to oral commensal bacteria may play a role, at least in part, in the maintenance of oral tissue integrity by attracting monocytes. [source] Histamine as an immune modulator in chronic inflammatory responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2007M. Jutel No abstract is available for this article. [source] | ||||||||||||||||||||||