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Multifunctional Cytokine (multifunctional + cytokine)
Selected AbstractsAnti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosusIMMUNOLOGY, Issue 3 2006Bailin Liang Summary Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from dysregulation of the immune system. Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, monocytes and T and B cells. It stimulates B-cell differentiation/maturation, immunoglobulin secretion, and T-cell functions. Elevated levels of IL-6 in serum, urine and renal glomeruli were detected in patients with active SLE and in murine models of SLE. Our study investigated the role of IL-6 in an SLE-like disease in New Zealand Black/White (NZB/W) F1 mice by administration of an anti-murine IL-6 monoclonal antibody (mAb). Intraperitoneal administration of the anti-IL-6 mAb suppressed the production of anti-dsDNA autoantibody. B-cell proliferation induced by anti-IgM and anti-CD40 was lower in the anti-IL-6 mAb-treated mice, ex vivo studies demonstrated that anti-IL-6 mAb treatment inhibited anti-dsDNA production. Anti-CD3-induced T-cell proliferation and mixed lymphocyte reactions were inhibited by anti-IL-6 mAb treatment, indicating a partial down-regulation of T cells. Histological analysis showed that treatment with anti-IL-6 mAb prevented the development of severe kidney disease. These results suggest that treatment with anti-IL-6 mAb has a beneficial effect on autoimmunity in murine SLE and that autoreactive B cells may be the primary target for anti-IL-6 mAb treatment; its effect on autoreactive T cells is also indicated. [source] Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patientsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2010A. Paradowska-Gorycka Summary Interleukin (IL)-10 is an important multifunctional cytokine with both anti-inflammatory and immunoregulatory effects in rheumatoid arthritis (RA). In the present study, we evaluated the frequency and potential impact of IL-10 promoter polymorphisms on susceptibility to and severity of RA in Polish in , patients with a high disease activity (mean DAS 28 C-reactive protein 5.25). DNA was obtained from 244 RA patients and 106 healthy controls. The ,592C/A and ,1082G/A IL-10 gene polymorphisms were amplified by polymerase chain reaction with restriction endonuclease mapping. The frequency of the IL-10-592CA, -592AA genotypes (respectively: 30% vs 5% and 7% vs 0%) and allele ,592A (37% vs 5%) were significantly higher in RA patients as compared with a control group. We did not find any association of the IL-10-592C/A genotype distribution with disease parameters, except for an increased ESR (erythrocyte sedimentation rate) in patients with the ,592CC genotype as compared with those with ,592CA or ,592AA genotypes (P = 0.01). The frequency of the IL-10-1082GG genotype was lower (P = 0.0001), and that of the IL-10-1082GA genotype was higher (P = 0.009) in RA patients comparing with the control group. In RA patients with ,1082GA or ,1082AA genotypes the time duration of the disease (P = 0.03), Health Assessment Questionnaire (HAQ) Score (P = 0.04) and PLT count (P = 0.001) were significantly increased as compared with subjects with ,1082GG genotype. Presented findings indicate that IL-10-592C/A and IL-10-1082G/A polymorphisms may be considered genetic risk factors for RA susceptibility and severity. [source] Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseasesJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2010J. H. Ross Ross JH, Hardy DC, Schuyler CA, Slate EH, Mize TW, Huang Y. Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. J Periodont Res 2010; 45: 688,694. © 2010 John Wiley & Sons A/S Background and Objective:, Epidemiological studies have established that patients with diabetes have an increased prevalence and severity of periodontal disease. Interleukin (IL)-6, a multifunctional cytokine, plays a role in the tissue inflammation that characterizes periodontal disease. Our recent study has shown a trend of increase in periodontal IL-6 expression at the mRNA level across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. However, the periodontal IL-6 expression at the protein level in these patients has not been investigated. Material and Methods:, Periodontal tissue specimens were collected from eight patients without periodontal disease and diabetes (group 1), from 17 patients with periodontal disease alone (group 2) and from 10 patients with both periodontal disease and diabetes (group 3). The frozen sections were prepared from these tissue specimens and IL-6 protein expression was detected and quantified. Results:, The nonparametric Kruskal,Wallis test showed that the difference in IL-6 protein levels among the three groups was statistically significant (p = 0.035). Nonparametric analysis using the Jonckheere,Terpstra test showed a tendency of increase in periodontal IL-6 protein levels across group 1 to group 2 to group 3 (p = 0.006). Parametric analysis of variance (ANOVA) on IL-6 protein levels showed that neither age nor gender significantly affected the difference of IL-6 levels among the groups. Conclusion:, Periodontal IL-6 expression at the protein level is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. [source] Histomorphometric characteristics and expression of epidermal growth factor and its receptor by epithelial cells of normal gingiva and hereditary gingival fibromatosisJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2003C. S. A. Araujo Objective:, The objective of this study was to examine the histomorphometric features and evaluate the expression of epidermal growth factor (EGF) and transmembranic receptor (EGFr) and the proliferative potential of epithelial cells from normal and hereditary gingival fibromatosis (HGF) gingival tissues. Background:, EGF is a multifunctional cytokine with a variety of biological effects including stimulation of cell proliferation by binding to its specific EGFr. Methods:, Immunohistochemistry was performed to measure EGF and EGFr expression and the epithelial cell proliferation was determined by measuring proliferating cell nuclear antigen (PCNA). Results:, Histomorphometric evaluation indicated that in HGF the mean height of the epithelial papillae was higher compared to the normal gingiva (NG), whereas mean epithelial area and number of epithelial papillae were quite similar in both groups. The EGF and EGFr positive cells were observed in the basal, spinous and granular cell layers of both normal and HGF tissues, with a gradual reduction from the basal layer. Although the expressions of EGF and EGFr in the control group were significantly higher than those from HGF, in HGF the epithelial papilla tips showed increased number of proliferating cells and elevated expression of EGF and EGFr. There was a correlation between the proliferative potential of epithelial cells and the expression of EGF or EGFr only in the epithelial papilla tips of HGF gingiva. Conclusion:, Our data suggest that EGF and EGFr in the oral epithelium of HGF gingiva may stimulate epithelial cell proliferation, with the resultant apical migration of the oral epithelium and formation of the slender deep epithelial papillae; however, without hyperplastic alterations. [source] Transient TWEAK overexpression leads to a general salivary epithelial cell proliferationORAL DISEASES, Issue 1 2009T Sugito Objectives:, Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that has pro-apoptotic, pro-angiogenic and pro-inflammatory effects. In liver, TWEAK leads to proliferation of progenitor oval cells, but not of mature hepatocytes. This study evaluated the hypothesis that TWEAK overexpression in salivary glands would lead to the proliferation of a salivary progenitor cell. Methods:, A recombinant, serotype 5 adenoviral vector encoding human TWEAK, AdhTWEAK, was constructed, initially tested in vitro, and then administered to male Balb/c mice via cannulation of Wharton's duct. TWEAK expression in vivo was monitored as protein secreted into saliva and serum by enzyme-linked immunosorbent assays. Salivary cell proliferation was monitored by proliferating cell nuclear antigen staining and apoptosis was monitored using TUNEL staining. Results:, AdhTWEAK administration led to a dose-dependent, transient TWEAK protein expression, detected primarily in saliva. Salivary epithelial cell proliferation was generalized, peaking on ,days 2 and 3. TWEAK expression had no detectable effect on apoptosis of salivary epithelial cells. Conclusion:, Transient overexpression of TWEAK in murine salivary glands leads to a general proliferation of epithelial cells vs a selective stimulation of a salivary progenitor cell. [source] Leukemia Inhibitory Factor: An Important Regulator of Endometrial FunctionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2004Zdzis, awa Kondera-Anasz Problem:, Leukemia inhibitory factor (LIF) is multifunctional cytokine that displays biological activities in different cells, including endometrial cells. The aim of this study is to describe implications of LIF on a physiological function of endometrium. Method of study:, The role of LIF in the endometrial function is reviewed and summarized from the available literature. Results:, LIF plays an important role in a physiological function of endometrium. In human endometrial LIF expression depends on cellular localizations, steroid hormones, menstrual stages and a local cytokine network. Stronger LIF expression exists in an endometrial epithelium during a luteal phase of the menstrual cycle, which coincides with the time of an implantation. The impairments of the endometrial LIF expression may play a significant role in the pathological processes involving implantation and the infertility. Conclusions:, There is a substantial evidence that LIF is a potential regulator of the endometrial function and might be one of the factors that play a key role in human reproduction. [source] In vivo IL-10 and TGF-, production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stabilityCLINICAL TRANSPLANTATION, Issue 2 2004Josefina Alberú Abstract:, Background:, Interleukin-10 (IL-10) and transforming growth factor-, (TGF-,) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-, by blood mononuclear cells correlates with excellent long-term graft function. Methods:, A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-, were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors. Results:, There was no correlation between IL-10 or TGF-, with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 ± 465, range 12.5,1929.3 pg/ml, and 189 ± 170, range 4.17,485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-, among the same groups (134.7 ± 79.2, range 68,421 pg/ml, and 121.4 ± 25.8, range 75,151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-, in kidney transplant recipients (p = 0.03). Conclusions:, The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-, and IL-10 may be of paramount importance in graft acceptance. [source] | ||||||||||