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Cytokine Responses (cytokine + response)
Kinds of Cytokine Responses Selected AbstractsCytokine response of electrolytic ablation in an ex vivo perfused liver modelANZ JOURNAL OF SURGERY, Issue 7-8 2010Gianpiero Gravante Abstract Background:, The inflammatory response following hepatic ablation depends on different factors including the method used, the duration and intensity of the treatment and the presence or absence of ischemia. Debate continues about the use of different modalities and whether some aspects of the response may be advantageous by releasing immunological active substances. Little data have been published concerning the cytokine response elicited by hepatic electrolytic ablation (EA). Study of an ex vivo liver model could allow for the evaluation of this response without the influence of confounding systemic factors. Methods:, Livers explanted from 11 pigs were perfused extracorporeally with normothermic autologous blood. Four of them underwent EA after 1 h of reperfusion. Serum samples were obtained up to 6 h after the reperfusion and assayed for IL-1,, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-,, TNF-,. Results:, Significant changes in the control group were observed for IL-6 after the second hour and IL-8 after the first hour compared with baseline levels (P < 0.001). In the EA group, IL-6 and IL-12 were raised after the second hour and IL-8 and IL-10 after the first hour (P < 0.001). The comparison between groups showed significant differences for IL-2, IL-4 (decreased in the EA group compared with controls), IL-10 and TNF-, (EA group increased compared with controls; P < 0.001). Conclusions:, The ex vivo perfused liver model demonstrated changes in levels of IL-2, IL-4, IL-10 and TNF-, following hepatic EA. [source] Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulinJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Christine Ma Abstract Viral loads and cytokine responses Epstein,Barr virus (EBV) were measured in an 18-year-old boy with severe glandular fever complicated by a mild anaemia, severe thrombocytopaenia and neutropaenia. Hepatosplenomegaly was detected by abdominal ultrasound in the presence of significant hepatitis. Cytokine testing demonstrated elevated cell-mediated Th1 (IFN-,, IL-12, sTNFR1, CXCL10, CXCL9 and CCL3) and humoral Th2 (IL-4) immune responses. Serum antibodies to EBV virus capsid antigen (VCA) IgM and IgG antibodies were detected, together with a raised EBV DNA level (up to about 70,000 DNA copies/mL) in the acute phase of the illness. This EBV DNA load decreased rapidly in response to treatment with a combination of foscarnet, intravenous immunoglobulin and prednisolone, and the boy's symptoms settled eventually after approximately 50 days of illness, following this combined antiviral and immune-modulating therapy. Detailed immunological, virological, haematological and biochemical laboratory parameters are presented to document this patient's severe EBV disease and eventual recovery. J. Med. Virol. 81:99,105, 2009. © 2008 Wiley-Liss, Inc. [source] Mechanical strain increases cytokine and chemokine production in bronchial fibroblasts from asthmatic patientsALLERGY, Issue 1 2009F. Le Bellego Background:, Mechanical strain and cytokine stimulation are two important mechanisms leading to airway remodeling in asthma. The effect of mechanical strain on cytokine secretion in airway fibroblasts is not known. The aim of this study was to determine whether bronchial and nasal fibroblasts differentially alter cytokine secretion in response to mechanical strain. Methods:, We measured secretion of the pro-fibrotic cytokine, interleukin-6 (IL-6), and the pro-inflammatory cytokines, IL-8 and monocyte chemotactic protein 1, before and after mechanical strain in bronchial fibroblasts obtained from asthmatic patients [asthmatic bronchial fibroblasts (BAF)] and normal volunteers [normal bronchial fibroblasts (BNF)], and in nasal fibroblasts (NF) obtained from nasal polyps. Cells were grown on flexible membranes and a mechanical strain of 30% amplitude, 1 Hz frequency was applied for 3, 6 and 24 h. Control cells were unstrained. IL-6, IL-8 and monocyte chemotactic protein 1 was measured after 24 h strain using enzyme-linked immunoassay; mRNA was measured by real time polymerase chain reaction. We also measured mRNA for versican, a matrix proteoglycan, known to be upregulated in the asthmatic airway wall. Results:, In unstrained conditions, no differences in cytokine secretion were observed. After 24 h strain, BAF secreted more IL-6 than BNF. Mechanical strain increased IL-8 mRNA in BAF, BNF and NF; and IL-6 and versican mRNA, in BAF, only. Conclusions:, Cytokine responses to mechanical strain varied in different airway fibroblast populations, and depended on the site of origin, and the underlying inflammatory state. Strain resulted in IL-6 upregulation and increased message for extracellular matrix protein in bronchial fibroblasts from asthmatic patients only, and may reflect these patients' propensity for airway remodeling. [source] Cytokine responses in immunized and non-immunized calves after Ostertagia ostertagi infectionPARASITE IMMUNOLOGY, Issue 9 2005E. CLAEREBOUT SUMMARY The objective of this study was to evaluate abomasal cytokine responses in helminth-naive calves and calves vaccinated with protective antigen fractions from Ostertagia ostertagi after an experimental challenge infection with infective third stage (L3) larvae. Abomasal lymph nodes and/or abomasal mucosa were collected and messenger RNA for the Th1 cytokines (IFN-,, IL-2, IL-12 p40 subunit), the Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, IL-15) and the Th3/Tr cytokine TGF-, was quantified by real-time RT-PCR. Vaccination had no effect on cytokine profiles in either the abomasal lymph nodes or the abomasal mucosa. However, following infection all calves showed a significant decrease in the Th1 cytokines, IFN-, and IL-12 p40, and a significant increase in the Th2 cytokines, IL-4, IL-5, IL-10 and IL-13 in the lymph nodes, compared to non-infected calves. No correlation between the Th2 response and protection induced by vaccination could be demonstrated. In contrast, a Th2 pattern was not observed in the mucosa of the infected calves, which exhibited an increase in IFN-, as well as in the Th2 cytokines IL-4, IL-5 and IL-10 mRNA. No significant association was observed in the abomasal mucosa between any examined cytokine mRNA level and immune effector responses such as parasite-specific antibodies or the number of mucosal mast cells or eosinophils. [source] Cytokine responses to mitogen and Schistosoma haematobium antigens are different in children with distinct infection historiesPARASITE IMMUNOLOGY, Issue 10 2001Janet T. Scott Prevalence of Schistosoma haematobium infection in children from two neighbouring villages in Zimbabwe was 77·1% and 40·3%, respectively. The age-intensity data indicated peak intensities of infection at a lower age in the high prevalence village. This study investigated whether the difference in infection histories was reflected in a difference in cytokine profiles between children resident in these two villages. Blood samples were taken to assay for cytokine secretion 1 year after treatment for schistosomiasis. They were cultured with phytohaemagglutinin (PHA), schistosome egg antigens (SEA) or cultured without stimulant and tested for the presence of interleukin (IL)-4, IL-5, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-,. Blood samples from children from the low prevalence village were more likely to produce IL-4 (P < 0·0001) and produced higher levels of IFN-, (P < 0·02) and GM-CSF (P < 0·03) when cultured with PHA for 24 h. Residence in the high prevalence village was associated with production of IL-10 (P < 0·006) and GM-CSF (P < 0·04) in response to culture with SEA and IL-5 (P < 0·02) with PHA for 48 h. The interaction between age and village was not significant for these results; however, there was a significant interaction between age and village for IL-5 detected in blood samples cultured with PHA for 24 h (P < 0·01). These results concur with previous observations that major patterns of cytokine production can be related to immunosuppression, but also indicate an underlying pattern which reflects the importance of history of infection to the immune response. [source] Methylisothiazolinones elicit increased production of both T helper (Th)1- and Th2-like cytokines by peripheral blood mononuclear cells from contact allergic individualsBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2003K. Masjedi Summary Background Delayed-type hypersensitivity reactions to nickel (Ni2+) in humans are associated with increased production of both T helper (Th) 1- and Th2-like cytokines. Cytokine responses to the major group of contact allergens, i.e. organic compounds, have been less extensively studied. We have investigated here the cytokine production induced by a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), the active ingredients in common preservatives that are capable of eliciting allergic contact dermatitis. Objective To characterize the immune response induced by MCI/MI in terms of the production of Th1- and Th2-like cytokines in peripheral blood mononuclear cells (PBMC) from allergic and non-allergic subjects. Methods Ten subjects with a history of contact allergy to MCI/MI and nine age-matched non-allergic volunteers participated. Their actual status was confirmed by patch testing. PBMC were cultured in the presence or absence of MCI/MI; cell proliferation was measured employing [3H]thymidine incorporation; and the number of cytokine-producing cells was determined using the enzyme-linked immunospot (ELISpot) assay and the levels of soluble cytokines in culture media by the enzyme-linked immunosorbent assay (ELISA). Results The proliferative response of PBMC to MCI/MI was significantly greater in the case of the allergic group than for the non-allergic group, as was the production of interleukin (IL)-2 and IL-13 (as determined by ELISpot and/or ELISA). PBMC from three of the allergic individuals with increased production of IL-2 and IL-13 responded to MCI/MI with elevated numbers of cells producing IL-4 and IL-5. The increases in the production of IL-2, IL-4, IL-5 and IL-13 were positively correlated. Conclusion MCI/MI elicited concomitant production of both Th1- and Th2-like cytokines by PBMC from subjects with contact allergy to these substances. This finding indicates that the organic compounds MCI/MI elicit a mixed Th1- and Th2-type of response, similar to that elicited by the metal ion Ni2+ in Ni2+ -sensitized individuals. [source] Cytokine responses to allergens during the first 2 years of life in Estonian and Swedish childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2006M. F. Böttcher Summary Background The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30,40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life. Objective To investigate the development of allergen-specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden. Methods The development of immune responses to food (,-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months. Results The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non-specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen-specific responses in the Estonian infants was less marked. These differences were particularly notable for birch-specific T cell responses, which correlated with development of atopic disease in the Swedish children. Conclusions The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations. [source] Irritant threshold and histological response of epidermis to irritant applicationCONTACT DERMATITIS, Issue 5-6 2004H. R. Smith Individuals vary in their ability to react to irritants, which can be demonstrated for sodium lauryl sulfate (SLS) using the irritant threshold (IT) test. We aimed to study whether the histological and immunohistochemical features of the skin following SLS exposure varied with subject's IT. 8 subjects were recruited. Their IT was measured. Biopsies were taken after 2 hr and 4 hr of occlusion with 20% SLS and control. The specimens were stained with haematoxylin and eosin and for Langerhans cells. At 4-hr, low-threshold subjects developed changes to a greater extent than high-threshold subjects. The relationship of histological reaction to IT could be related to a differential pro-inflammatory cytokine response in subjects. Low IT has been previously associated with a tumour necrosis factor alpha promoter region polymorphism. [source] Polypropylene glycol is a selective binding inhibitor for LTA and other structurally related TLR2 agonistsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008Christian Draing Abstract Polypropylene glycol (PPG) is commonly added to bacterial cultures to avoid foaming. However, lipoteichoic acid (LTA) from bacteria grown with PPG lacked cytokine-inducing potency in human blood. We tested the blocking efficacy of several glycols on the cytokine response to staphylococcal LTA in human blood. PPG 1200 was the most potent inhibitor tested, shown for TNF, IL-1,, IL-6, IL-8, IL-10 and TGF-, induction, and displayed no cytotoxic effects. TNF induction by Staphylococcus aureus or by Toll-like receptor (TLR)2 agonists (di- and triacylated lipopeptides and LTA) was also inhibited by PPG 1200, but not that induced by Escherichia,coli or TLR4 agonists. In flow cytometric studies, PPG-carrying nanobeads bound more rhodamine-labeled LTA than those with glycerol. Additionally, the methyl group peak in the 1H-NMR of LTA shifted after incubation with increasing PPG 1200 concentrations. Sequential incubation of polystyrene plates with LTA, then PPG 1200 and then blood, with washing steps in between, showed that LTA-induced TNF release was inhibited. But when PPG 1200 was pre-incubated with blood that was washed before LTA was added, TNF induction was not repressed, demonstrating that PPG binds LTA and not cellular structures. In summary, PPG 1200 is a novel inhibitor of cytokine induction by TLR2 agonists, which interferes directly with the ligands. [source] MR1-restricted V,19i T cells , a second population recognizing lipid antigens?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Jens Schümann Abstract There is increasing evidence that T cells recognizing lipid antigens contribute to the immunological regulation of different disease conditions including autoimmunity. The best-known subset is CD1d-restricted lipid-reactive T cells characterized by the expression of an invariant TCR, chain. Much less is known about the biology of another invariant T cell subset, which is restricted to the MHC class I-like molecule MR1. A beneficial role of MR1-restricted T cells has been suggested in a mouse EAE model. However, the nature of antigens that can be presented by MR1 to this invariant T cell subset remained largely unclear. An article in this issue of the European Journal of Immunology presents strong indications that derivatives of ,-mannosyl ceramide (,-ManCer), i.e. glycolipids, can serve as ligands for MR1-restricted invariant T cells. In addition to that, the structure of the ,-ManCer sphingosine chain influences the Th1-Th2 polarization of the cytokine response. These important new findings will foster further research on the identity of physiological ligands for MR1-restricted T cells and on their relation with immunoregulation. See accompanying article: http://dx.doi.org/10.1002/eji.200636689 [source] Deficient translocation of c-Rel is associated with impaired Th1 cytokine production in T cells from atopic dermatitis patientsEXPERIMENTAL DERMATOLOGY, Issue 1 2005Karsten Dieckhoff Abstract:, Decreased production of T helper type 1 (Th1) cytokines, such as interferon-, (IFN-,) or interleukin-2 (IL-2), is a hallmark of atopic diseases. While accessory signals from antigen-presenting cells may be missing, T cells themselves may be suppressed in their ability to produce substantial amounts of Th1 cytokines. We show, in this study, that T cell receptor (TCR)-activated T cells from atopic dermatitis (AD) patients proliferate less than control T cells and produce lower amounts of IFN-, and IL-2, but comparable amounts of IL-4. Because mice lacking the nuclear factor kappa B (NF-,B) transcription factors , p65 or c-Rel , show reduced Th1, but undisturbed Th2 responses, we investigated the role of c-Rel and p65 for Th1 cytokine production in T cells from healthy and severe AD patients. TCR-activated primary T cells from healthy donors treated with c-Rel antisense oligonucleotides produced lower levels of IL-2 and IFN-, and proliferated less efficiently than the corresponding control T cells. Moreover, transfection of primary T cells with c-Rel or p65 enhanced proliferation and production of IL-2 and IFN-,. Nuclear extracts of activated primary T cells from AD donors bound weakly to NF-,B-specific oligonucleotides, compared to extracts from healthy control T cells. Western blotting studies revealed that nuclear, but not cytosolic, extracts from T cells of AD patients lacked significant amounts of c-Rel and p65. T cell clones derived from AD patients failed to sufficiently translocate c-Rel and p65 into the nucleus following activation. Thus, impaired nuclear translocation of c-Rel and p65 may determine an impaired Th1 cytokine response in AD. [source] Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complexHEPATOLOGY, Issue 3 2002David E. J. Jones Bacterial DNA containing unmethylated CpG dinucleotide motifs is immunostimulatory to mammals, skewing CD4+ T-cell responses toward the Th1 phenotype. Autoreactive T-cell responses seen in primary biliary cirrhosis (PBC) are typically of the Th1 phenotype, raising the possibility that bacterial DNA might play a role in the generation of pathologic autoimmunity. We therefore studied the effects of CpG motif-containing oligodeoxynucleotides (ODN) on responses to pyruvate dehydrogenase complex (PDC, the autoantigen in PBC) in a murine model. Sensitization of SJL/J mice with non,self-PDC has been shown to result in induction of autoreactive T-cell responses to PDC sharing characteristics with those seen in patients with PBC. Administration of CpG ODN to SJL/J mice at the time of sensitization with PDC resulted in a significant skewing of splenic T-cell response to self-PDC, with significant augmentation of the Th1 cytokine response (interleukin [IL] 2 and interferon [IFN] gamma) and reduction of the Th2 response (IL-4 and IL-10). In fact, CpG ODN seemed to be more effective at biasing the response phenotype and as effective at inducing liver histologic change as complete Freund's adjuvant (CFA), the standard adjuvant used for induction of Th1 responses in murine autoimmune and infectious immunity models. In conclusion, our findings raise the possibility that bacteria play a role in the development of autoimmunity (in PBC at least) through the potential of their DNA to shift the T-cell responses toward the phenotype associated with autoimmune damage. Moreover, this study suggests caution in the therapeutic use of CpG ODN as vaccine adjuvants. [source] Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosisHEPATOLOGY, Issue 2 2001Monica G. Chiaramonte In several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity and mortality. Here, using a model of infection-induced liver fibrosis, we show that interleukin (IL)-13 is required at all stages of Schistosomiasis mansoni infection to induce fibrosis. IL-4 production was preserved in IL-13,deficient mice, yet failed to significantly contribute to the fibrotic response in either acute or chronic infection. Significant fibrosis develops in all infected mice, although the magnitude of the response varies widely in inbred mice. C3H/HeN, BALB/c, and C57BL/6 mice develop high, intermediate, and low levels of fibrosis, respectively. Despite these differences, IL-13 antagonism resulted in a marked amelioration of fibrosis in all strains. The fibrotic mechanism in the high- and low-responder strains was unrelated to their tissue eosinophil or mast cell responses, but did correlate with their patterns of IL-13, IL-10, and interferon gamma (IFN-,) mRNA expression. Indeed, severe fibrosis correlated with a high IL-13 and low IFN-,/IL-10 mRNA response. Because fibrotic diseases are typically progressive disorders, an important issue was to determine whether IL-13 inactivation might be used to treat an established and ongoing fibrotic disease. Here, IL-13 antagonism was highly efficacious, even after fibrosis and the Th2 cytokine response were firmly established. These studies demonstrate the central role played by IL-13 in fibrogenesis and suggest that therapeutic approaches aimed at disrupting the IL-13 pathway will be highly effective at preventing fibrotic disease caused by chronic Th2-mediated inflammatory reactions. [source] Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCGIMMUNOLOGY, Issue 1pt2 2009Hai-Feng Ou-Yang Summary Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette,Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-, (IFN-,) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4+ CD25+ Foxp3+ T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4+ CD25+ T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-, (TGF-,)-producing CD4+ CD25+ Foxp3+ regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma. [source] Anti-inflammatory role of interleukin-15 in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2005Manuel A Silva MD Abstract Background: Interleukin (IL)-15 is overexpressed in intestinal tissue with active Crohn's disease (CD). However, its role in the pathogenesis of the disease remains uncertain. We studied the effects of IL-15 on colonic mucosal proinflammatory cytokine response in vitro using organ culture of human colonic explants. Methods: Colonic tissue was obtained from (1) resections in pediatric CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary experiments, explants from the resections were cultured in the presence or absence of a simulated TH1 stimulation using ionomycin (Io) and phorbol-myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal biopsies were cultured in the same conditions as above, with or without adding a monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)-,, tumor necrosis factor (TNF)-,, and IL-2R, were measured by enzyme-linked immunosorbent assay. Results: IL-15, in the absence of Io + PMA, did not induce the expression of IFN-,, TNF-,, or IL-2R,. Only inflamed explants from resections stimulated with Io + PMA expressed IFN-,, TNF-,, and IL-2R,. This TH1 stimulatory effect was inhibited by IL-15 in a dose-dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and control tissue responded to stimulation with Io + PMA (P < 0.05) with increased IFN-, and TNF-, (P < 0.05). This response was again inhibited by IL-15. The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P < 0.05). The data for the CD group were also analyzed according to the severity of colonic inflammation and medication use. Conclusions: Our results suggest a possible anti-inflammatory role for IL-15 in CD. We postulate that its overexpression in CD potentially represents a protective mechanism against the exaggerated TH1 immune response. [source] Predominant T helper type 2-inflammatory responses promote murine colon cancersINTERNATIONAL JOURNAL OF CANCER, Issue 9 2006Emi Osawa Abstract Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-,) gene deficient (,/,) [Th2 dominant] or interleukin (IL)-4,/, [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirty-three weeks after initial treatment, the total colon was examined. When IFN-,,/, mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 ± 1.7) than in WT (3.3 ± 2.9) or IL-4,/, (3.1 ± 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-,,/, mice than in IL-4,/, mice. Histologically, the tumors were well- or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-,,/, mice showed distinct nuclear expression of ,-catenin, in contrast to the strong membrane staining seen in tumors of IL-4,/, mice. In conclusion, colonic inflammation associated with Th2-donimant cytokine responses enhanced the formation of malignant neoplasms. © 2005 Wiley-Liss, Inc. [source] The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2003C. Büning Summary Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11,12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype,phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases. [source] Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infectionJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001P. Hofmann Abstract Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is accompanied by an intense mononuclear leukocyte infiltration. Because myocardial tissue damage may either result from viral infections or from a dysregulated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived macrophages yielded a low amount of new viruses, which led to cell death. Although CVB3 infection induced the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF-,), interleukin (IL)-1, and IL-6, only little cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persistently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macrophages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy. J. Med. Virol. 64:487,498, 2001. © 2001 Wiley-Liss, Inc. [source] The Immune,Endocrine Interaction Varies with the Duration of the Inflammatory Process in Cardiac Surgery PatientsJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2000A. Roth-Isigkeit The present study investigated the perioperative course of cytokine release and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to the duration of the inflammatory response in cardiac surgery patients. Twelve male patients scheduled for elective coronary artery bypass grafting surgery with cardiopulmonary bypass and general anaesthesia were divided into two study groups: group 1 (n=6) underwent surgery at 13.00 h±30 min, group 2 (n=6) at 08.30 h±50 min. Blood samples were collected preoperatively and up to the first postoperative day. Postoperatively, on the day of surgery, serum concentrations of the proinflammatory cytokines interleukin (IL)-6, IL-1, and tumour necrosis factor (TNF)- , were not significantly different between the two groups, while blood concentrations of cortisol, adrenocorticotrophic hormone (ACTH) and , -endorphin in group 2 patients were significantly higher than in group 1 patients. Postoperatively, on the day of surgery, ACTH and cortisol concentrations in group 1 patients were positively correlated to the blood concentrations of IL-1,, IL-6 and TNF- ,. By contrast, group 2 patients showed no significant relationship between cytokine release and activation of HPA axis at this time. Our results suggest that in patients undergoing cardiac surgery, the cytokine response is initiated before the HPA axis is fully activated. In the early postoperative period, cytokines appear to be involved in the activation of the HPA axis, while in the later postoperative period, high cortisol concentrations may inhibit the release of IL-6. [source] Less systemic cytokine response in patients following microendoscopic versus open lumbar discectomyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2005Tsung-Jen Huang Abstract The magnitude of the tissue damage from surgery impacts the trauma response. This response is proportional to the severity of surgical stress. Systemic cytokines are recognized as markers of postoperative tissue trauma. Microendoscopic discectomy (MED) recently has become popular for treating lumbar disc herniations, and is associated with favorable clinical outcomes compared with open discectomy (OD). This study postulates that MED is a less traumatic procedure, and therefore has a lower surgical stress response compared to OD. In this study, a quantitative comparison of the overall effects of surgical trauma resulting from MED and OD was performed through analyzing patient systemic cytokines response. From April, 2002 to June, 2003, 22 consecutive patients who had symptomatic lumbar disc herniations were prospectively randomized to undergo either intracanalicular MED (N = 10) or OD (N = 12). In this study, the Vertebroscope System (Zeppelin, Pullach, Germany) was used to perform the endoscopic discectomy procedure in all MED patients. Serum levels of tumor necrosis factor-, (TNF-,), Interleukin-1, (IL-1,), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) were measured before surgery and at 1, 2, 4, 8 and 24h after surgery using an enzyme-linked immunosorbent assay. Serum C-reactive protein (CRP) was measured at the same time interval. The results showed the MED patients had shorter postoperative hospital stay (mean, 3.57 ± 0.98 vs. 5.92 ± 2.39 days, p = 0.025) and less intraoperative blood loss (mean. 87.5 ± 69.4 vs. 190 ± 115 ml, p = 0.042). The operating length, including the set-up time, was longer in the MED group (mean, 109 ± 35.9 vs. 72.1 ± 17.8 min, p = 0.01). The mean size of skin incision made for the MED patients was 1.86 ± 0.13cm (range 1.7,2.0cm); and 6.3 ± 0.98 cm for the OD patients (range 5.5,8cm), p = 0.001. The patients' pain severity of the involved limbs on 10-point Visual Analog Scale before operation in MED group was 7.5 ± 0.3 (range 6,9) and 8 ± 0.2 (range 7,9) in OD group, p = 0.17; and after surgery, 1.5 ± 0.2 (range 1,2) in MED group and 1.4 ± 0.1 (range 1,3) in OD group, p = 0.91. CRP levels peaked at 24h in both groups, and OD patients displayed a significantly greater postoperative rise in serum CRP (mean, 27.78 ± 15.02 vs. 13.84 ± 6.25mg/l, p = 0.026). Concentrations of TNF-,, IL-1,, and IL-8 were detected only sporadically. Serum IL-6 increased less significantly following MED than after OD. In the MED group, IL-6 level peaked 8 h after surgery, with the response statistically less than in the open group (mean, 6.27 ± 5.96 vs. 17.18 ± 11.60pg/ml, p = 0.025). A statistically significant correlation was identified between IL-6 and CRP values (r = 0.79). Using the modified MacNab criteria, the clinical outcomes were 90% satisfactory (9/10) in MED patients and 91.6% satisfactory (11/12) in OD patients at a mean 18.9 months (range 10,25) follow-up. Based on the current data, surgical trauma, as reflected by systemic IL-6 and CRP response, was significantly less following MED than following OD. The difference in the systemic cytokine response may support that the MED procedure is less traumatic. Moreover, our MED patients had achieved satisfactory clinical outcomes as the OD patients at a mean 18.9 months follow-up after surgery. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Anesthesiologists at work: an increase in pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responsesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2006B. Beilin Background:, Anesthesiologists are a population at high risk of alcohol and drug abuse, depression, suicide, and psychiatric hospitalization. The impact of their working milieu on specific immune indices has scarcely been studied, and it is assumed that immune perturbations may contribute to some of the above risks. This study took advantage of an unplanned, 3-month long strike of anesthesiologists, and explored its relations to specific immune measures. Methods:, We assessed induced cytokine production and lymphocytes proliferative responses in blood samples taken from 10 anesthesiologists just before the strike and at its end, after a long period of markedly reduced workload. Results:, The results indicated that the proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly lower at the end of the strike. At this time point, we observed a significant decrease in the production of interleukin-6 (IL-6), IL-10 and IL1ra levels, and a significant increase in IL-2 production. A strong trend towards a decline in tumor necrosis factor-, (TNF-,) levels was evident, while levels of IL-1, were unchanged. Conclusion:, These findings suggest that the working conditions of anesthesiologists are associated with specific immune alterations, including a shift towards a Th2 cytokines' dominance, and an elevated pro-inflammatory cytokine response. A reduced Th1 profile has been related to increased susceptibility to infections, and high pro-inflammatory cytokine levels were recently proposed as etiological factors in cardiovascular diseases and in depression. [source] Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro modelACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2006S. Ziegeler Background:, Sepsis may lead to the suppression of stimulated cytokine release after Gram-negative stimuli, correlating with a fatal outcome. Treatment of sepsis includes adequate therapy with antibiotics. The aim of this study was to investigate the role of antibiotics in the modulation of the lipopolysaccharide (LPS)-stimulated cytokine response of human monocytes. Methods:, In this ex vivo, in vitro study, whole blood samples were taken from 10 healthy volunteers, stimulated with LPS in the presence or absence of various antibiotics (penicillin, amoxicillin, cefuroxime, ceftazidime, cefotaxime, piperacillin/tazobactam, imipenem/cilastatin, gentamicin, netilmicin, ciprofloxacin, vancomycin) and cultured for 24 h. Thereafter, tumor necrosis factor-, (TNF-,) and interleukin-10 (IL-10) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, CD14 and HLA-DR expression on monocytes was assessed using flow cytometry. Results:, All cephalosporins decreased LPS-stimulated IL-10 release. Cefuroxime and cefotaxime also decreased the expression density of the LPS recognition molecule CD14 on monocytes. An increase in LPS-stimulated IL-10 release was observed with vancomycin. A suppression of LPS-stimulated TNF-, and IL-10 release was observed in the presence of ciprofloxacin. Conclusion:, These results indicate a modulation of the expression density of CD14 on monocytes, together with a shift from a balanced to an inflammatory cytokine release pattern, by cefuroxime and cefotaxime. Vancomycin changes the response to an anti-inflammatory release pattern. After ciprofloxacin, a profound unresponsiveness of immune-competent cells to LPS stimulation is observed. Because of the critical role of a balanced innate immune response, these data may be of importance for the selection of antibiotics in septic patients. [source] Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine responseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010Y. ROTMAN Aliment Pharmacol Ther,31, 1018,1027 Summary Background, Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses. Aim, To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses. Methods, A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 ,g/week) and 27 patients with standard doses (180 ,g/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated. Results, Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups. Conclusion, A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing. [source] Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profilesJOURNAL OF VIRAL HEPATITIS, Issue 8 2009T. N. Q. Pham Summary., Hepatitis C virus (HCV) replicates in immune cells in both chronic hepatitis C (CHC) and occult HCV infection, but the extent of virus replication in this compartment in these opposing infection forms varies greatly. It was unknown whether this could be linked to HCV genotype or to differences in host gene expression shaping the immune response, and whether HCV replication in immune cells is sensitive to endogenous antiviral cytokines. In this study, we uncovered that significantly greater HCV load in peripheral blood mononuclear cells (PBMC), but not in plasma, coincided with HCV genotypes 2 and 3 in CHC, but with genotype 1 in residual occult infection after clinical resolution of hepatitis C. Moreover, PBMC from individuals with occult infection transcribed significantly greater levels of IFN-,, IFN-, and TNF-,, but less interleukin (IL)-10 than those from CHC. In CHC, PBMC with low HCV load expressed significantly more IFN-, but less IL-12 than did cells with high virus content. In occult infection, HCV RNA detection in PBMC was associated with much lower IFN-, and IL-12 expression. Further, HCV replication in T lymphocytes could be completely eliminated by activation of endogenous IFN-, in CHC, but of IFN-, in occult infection. In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-,, IFN-, and TNF-,, is associated with a more robust HCV replication in immune cells. [source] Effects of sevoflurane and desflurane on cytokine response during tympanoplasty surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2005G. M. Koksal Background:, This study was devised to compare the effects of sevoflurane and desflurane anaesthesia on the cytokine response. Methods:, Sixty ASA I,II patients, scheduled for tympanoplasty, were randomly allocated to be anaesthetized with either sevoflurane or desflurane at maintenance inspiratory concentrations of 1,1.5 MAC of either agent. Blood samples were taken for plasma tumour necrosis factor , (TNF,), interleukin 1, and interleukin-6 assay before induction of anaesthesia, before surgery, and at the end of surgery. Alveolar cells were obtained after induction of anaesthesia and at the end of surgery. Results:, Plasma TNF, was greater with desflurane than sevoflurane both before surgery (45.1 ± 3.5 pg ml,1 for desflurane vs. 23.2 ± 2.5 pg ml,1 for sevoflurane, P < 0.01) and (62.0 ± 5.3 pg ml,1 vs. 35.5 ± 4.6 pg ml,1, P < 0.001). Interleukin 1, was similarly greater with desflurane than sevoflurane before (39.3 ± 4.0 pg ml,1 vs. 17.4 ± 3.0 pg ml,1; P < 0.01) and after surgery (46.0 ± 3.4 pg ml,1 vs. 23.3 ± 3.2 pg ml,1, P < 0.001). There were similar results for interleukin 6 before (42.3 ± 3.5 pg mls,1. 29.0 ± 2.6 pg ml,1, P < 0.001) and after surgery (86.0 ± 4.5 pg ml,1 vs. 45.9 ± 6.3 pg ml,1, P < 0.001). Alveolar cell TNF, concentrations after surgery were also greater with desflurane than sevoflurane (96.3 ± 12.4 pg ml,1 vs. 64.8 ± 10.1 pg ml,1, P < 0.001), as were interleukin 1, (75.4 ± 6.2 pg ml,1 vs. 32.0 ± 8.3 pg ml,1, P < 0.001) and interleukin 6 concentrations (540.1 ± 65.3 pg ml,1 vs. 363.6 ± 29.2 pg ml,1, P < 0.001). Conclusion:, Desflurane appears to cause a greater systemic and intrapulmonary pro-inflammatory response than sevoflurane during anaesthesia for ear surgery. [source] General and specific host responses to bacterial infection in Peyer's patches: a role for stromelysin-1 (matrix metalloproteinase-3) during Salmonella enterica infectionMOLECULAR MICROBIOLOGY, Issue 1 2007Scott A. Handley Summary Salmonella enterica serovar Typhimurium (S. typhimurium) and Yersinia enterocolitica are enteric pathogens capable of colonizing and inducing inflammatory responses in Peyer's patches (PPs) and mesenteric lymph nodes (MLNs). Although the tissue colonization pattern is similar between these two pathogens, their pathogenic lifestyles are quite different. For example, while S. typhimurium is primarily an intracellular pathogen, Y. enterocolitica survives primarily extracellularly. We determined and compared the transcriptional changes occurring in response to S. typhimurium and Y. enterocolitica colonization of PP using Affymetrix GeneChip technology. Both pathogens elicited a general inflammatory response indicated by the upregulation of cytokines and chemokines. However, specific differences were also observed, most notably in the transcriptional regulation of gamma interferon (IFN-,) and IFN-,-regulated genes in response to S. typhimurium but not Y. enterocolitica. Of particular note, a group of genes encoding matrix metalloproteinases (MMPs) had increased transcript numbers in the PPs following infection with both pathogens. The experiments described here compare oral S. typhimurium or Y. enterocolitica infection in stromelysin-1 (MMP-3)-deficient mice (mmp-3,/,) with mice possessing functional MMP-3 (mmp-3+/+). There was little difference in the survival of MMP-3-deficient mice infected with Y. enterocolitica when compared with littermate controls. Surprisingly though, mmp-3,/, mice were markedly more resistant to S. typhimurium infection than the control mice. S. typhimurium was able to colonize mmp-3,/, mice, albeit in a delayed fashion, to equivalent levels as mmp-3+/+ mice. Nevertheless, significantly lower levels of inflammatory cytokines were detected in tissues and serum in the mmp-3,/, mice in comparison with mmp-3+/+ mice. We hypothesize that MMP-3 is involved in initiating an early and lethal cytokine response to S. typhimurium colonization. [source] Role for CTLA-4 but not CD25+ T cells during Schistosoma mansoni infection of micePARASITE IMMUNOLOGY, Issue 6 2007C. M. WALSH SUMMARY Schistosoma mansoni infection of mice increases the frequency of cells that are CD4+CD25+ in the acute (4 and 8 weeks) and chronic (16 week) stages of infection. Depletion of > 85% of CD25+ cells in the acute or chronic stages of schistosome infection caused no overt changes in morbidity or immunological responses. The absence of effect in mice with CD25+ cells depleted may be due to the preferential expression of IL-4 and IL-10, two cytokines that are protective in schistosome infection, on CD25, CD4+ cells. We also assessed infection-induced changes of other regulatory markers, GITR, CD103 and CTLA-4 on CD4+ cells. We identified a marked expansion of CTLA-4+ population on CD25, CD4+ cells in acute and chronic infection. Blocking of CTLA-4 during acute, but not chronic infection, caused significant weight loss and altered the type 2 cytokine response of mice, with increased IL-4 and IL-5 production associated with significantly more Th2 cells and eosinophils in the liver granuloma. This study illustrates the complexity of regulation of T cells in schistosome infection and highlights a specific role for CTLA-4+, but not CD25+ cells, in the regulation of Th2 responses in helminth infection. [source] Differential immunoglobulin E and cytokine responses in BALB/c and C57Bl/6 mice during repeated infections with blood-stage Plasmodium chabaudi malariaPARASITE IMMUNOLOGY, Issue 4 2000Helena Helmby Repeated blood-stage Plasmodium chabaudi chabaudi AS challenge infections in BALB/c and C57Bl/6 mice result in increased serum immunoglobulin (Ig) E levels and splenic cytokine production. The genetic background of the host influences both the cytokine response as well as the development of IgE antibodies. BALB/c mice showed high interleukin (IL)-4 secretion from splenocytes after in-vitro stimulation with malaria antigen after repeated P. chabaudi challenges and this was closely followed by higher levels of total IgE. Despite slightly elevated serum IgE levels, splenocytes from C57Bl/6 mice did not secrete any detectable IL-4 but produced interferon (IFN)-, in response to malaria antigen-stimulation in vitro. These data suggest that induction of IgE antibodies during murine malaria infection is genetically regulated. [source] High levels of CXCL8 in tracheal aspirate samples taken at birth are associated with adverse respiratory outcome only in preterm infants younger than 28 weeks gestationPEDIATRIC PULMONOLOGY, Issue 3 2007Jozef De Dooy PhD Abstract We investigated the relation between perinatal endotracheal colonization, the associated cytokine response and respiratory outcome in ventilated preterm neonates. Between September 1999 and March 2002, a cohort of 141 neonates with a gestational age <31 weeks requiring ventilation directly after birth, were followed prospectively. All were admitted to the Neonatal Intensive Care Unit, University Hospital of Antwerp, Belgium. A tracheal aspirate (TA) sample was collected soon after birth and was processed for microbiological examination, leukocyte count, and cytokine analysis (interleukines [IL] IL-1,, IL-6, CXCL8 (formerly called IL-8), IL-10, IL-12p70 and tumor necrosis factor alpha [TNF-,]). Together with the prospectively registered patient's comorbidities and severity of disease, these inflammatory parameters were analyzed in a multivariate Cox proportional hazards model with time of extubation and duration of oxygen therapy as main outcome measures. Of the 141 patients included, 31 (22%) died before discharge from the unit and 37 (26%) had a positive TA culture. Independent predictors of duration of mechanical ventilation were: gestational age <28 weeks, degree of respiratory distress syndrome (RDS) at birth, significant patent ductus arteriosus (PDA), the SNAP-score, and high levels of CXCL8 (>4,153 pg/ml) in TA only in neonates with a gestational age <28 weeks. Variables associated with extended duration of oxygen therapy were gestational age <28 weeks, birth weight <1,000 g, degree of RDS at birth, and duration of mechanical ventilation. Pediatr Pulmonol. 2007; 42:193,203. © 2007 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2009Melissa J. Mulla Problem:, The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast. Method of Study:, The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with ,-D-glutamyl- meso -diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR. Results:, Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NF,B inhibitor and a TLR4-dominant negative (DN). Conclusion:, This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NF,B pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins. [source] | ||||||||||||||||||||||||||||||||||