Evaluation of immune inhibitory cytokine profiles in epithelial ovarian carcinoma
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The aim of this study was to detect expression of different cytokines in epithelial ovarian carcinoma (EOC) cells and normal ovarian surface epithelial (OSE) cells in vitro and the levels of those with elevated expression in the EOC patients, and to analyze the contribution of cytokine profiles to tumor immune deficiency.Cytokine antibody array was used to detect cytokine profiles in two cell lines of EOC (SKOV3 and CaoV3), primarily cultured EOC and OSE cells. The levels of leukemia inhibitory factor (LIF), interleukin-10 (IL-10), IL-4, and transforming growth factor-beta1 (TGF-beta1) in peritoneal fluids and sera in the patients with EOC and benign gynecological tumors were detected by enzyme-linked immunosorbent assay.The levels of LIF, IL-10, and IL-4 were detected two times higher in the culture supernatants of the EOC cell lines than those in OSE cells by cytokine antibody array. Both LIF and IL-10 levels were more increased in ascites of EOC patients than in those in benign gynecological tumor patients (P < 0.05). The level of IL-4 was not detectable in any samples of ascites or sera. No difference of TGF-beta1 value was detected between patients with EOC and benign gynecological tumors.Epithelium ovarian carcinoma cells can produce more LIF, IL-10 and IL-4 than OSE cells, and contribute to the elevated levels of those cytokines in EOC patients, which probably participates in the development of immune deficiency in the peritoneal cavity of EOC patients.Oncostatin M
Ciliary neurotrophic factor
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Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both fat and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not involve the induction of these cytokines.
Ciliary neurotrophic factor
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Objective: This study aimed to determine oncostatin M (OSM), interleukin-11 (IL-11), and leukemia inhibitory factor (LIF) levels in gingival crevicular fluid (GCF), saliva, and serum in periodontally healthy individuals and those with gingivitis (G) and chronic periodontitis (CP) before and after periodontal treatment and to evaluate the relationship between these cytokine levels and clinical periodontal parameters.Materials and Methods: This study involved 24 patients with healthy (H) periodontal tissues, 24 patients with G, and 24 patients with CP.Initially, GCF, saliva, and serum samples were collected, and clinical periodontal measurements, including the plaque index, gingival index, probing depth, and clinical attachment levels, were recorded.At 8 weeks after the initial periodontal treatment, the abovementioned parameters were recorded in the G and CP groups.Cytokine levels were determined using enzyme-linked immunosorbent assay.Results: OSM levels in the GCF, saliva, and serum were significantly higher in the CP group (p<0.05)than in other groups.LIF levels in GCF exhibited a significant increase (p<0.05) in the CP group; however, no significant difference was found in the serum and saliva LIF levels among groups (p˃0.05).IL-11 levels were significantly higher in the CP group (p<0.05)than in other groups, but no significant difference was noted in the serum IL-11 levels among the groups (p˃0.05).Similarly, saliva IL-11 levels were significantly higher in the CP group than in the H group (p<0.05),but they did not show significant difference between the CP and G groups (p˃0.05).Comparative analysis of GCF, saliva OSM, and IL-11 levels in the G and CP groups before and after initial periodontal therapy revealed that they are significantly lower in both groups after therapy (p<0.05).Conclusion: Levels of OSM, LIF, and IL-11 are higher in the G and CP groups, which indicate periodontal tissue destruction.Decreases in IL-11, OSM, and LIF levels after treatment support the idea that initial periodontal therapy can inhibit periodontal tissue destruction.
Oncostatin M
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We investigated the serum concentration of interleukin-6 (IL-6) and the IL-6 family of cytokines (leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) using an enzyme-linked immunosorbent assay (ELISA) in 64 patients with systemic lupus erythematosus (SLE) and 15 healthy controls. We also examined a possible association between the serum levels of these proteins and SLE activity as well as correlations between the IL-6 concentration and the levels of LIF, OSM and CNTF. IL-6 was detectable in all 64 patients with SLE and normal individuals, and the level of this cytokine was significantly higher in patients than in the control group (p < 0.002 ). LIF, OSM and CNTF were detectable in 9 (14.1%), 6 (9.4%) and 51 (78%) patients, respectively, and undetectable in the majority of healthy individuals. We found positive correlation between the serum concentrations of IL-6, LIF, OSM and CNTF and SLE activity. IL-6 and OSM serum levels were also correlated but not IL-6 and LIF or CNTF. In conclusion, an increase in the serum levels of IL-6 and, to a lesser extent of LIF, OSM and CNTF concentrations may be useful markers for SLE activity.
Oncostatin M
Ciliary neurotrophic factor
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Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.
Oncostatin M
Glycoprotein 130
Ciliary neurotrophic factor
Interleukin-6 receptor
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Abstract Objective. To determine the expression of interleukin‐6 (IL‐6), IL‐11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL‐6‐type cytokines and C‐reactive protein (CRP). Methods. Messenger RNA (mRNA) and protein levels for IL‐6, IL‐11, LIF, and OSM were determined by using reverse transcription‐polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. Results. Cells isolated from the synovium of RA patients expressed mRNA for IL‐6, IL‐11, LIF, and OSM at higher levels than did synovial cells from osteoarthritis (OA) patients, and spontaneously released greater quantities of these proteins in culture. Fibroblast cell lines derived from RA synovium were able to produce IL‐6, IL‐11, and LIF, but not OSM, when stimulated with IL‐1 and tumor necrosis factor α. OSM was found to be produced spontaneously by synovial tissue macrophages. IL‐6, IL‐11, LIF, and OSM were present in synovial fluid from the RA patients; levels of IL‐6, LIF, and OSM were present in significantly greater quantities in RA patients than in OA patients. However, only IL‐6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, while other IL‐6‐type cytokines were not detected. Conclusion. IL‐6, IL‐11, LIF, and OSM are all produced in large amounts at the site of disease activity, but IL‐6 derived from synovial fibroblasts may be the major hormone‐like mediator that induces the hepatic synthesis of acute‐phase proteins in RA.
Oncostatin M
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Ciliary neurotrophic factor
Oncostatin M
Glycoprotein 130
Interleukin-6 receptor
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Oncostatin M
Hematology
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Despite of long-lasting efforts, in more than 50% of cases, the etiology of recurrent spontaneous abortion (RSA) remains unknown. Leukemia inhibitory factor (LIF) has an essential role in the reproductive process, such as modulating inflammatory responses. This study aimed to evaluate the relationship between the LIF gene expression as well as serum levels of inflammatory cytokines and occurrence of RSA in infertile women with a history of RSA.In this case-control study, the relative gene expression levels of LIF, concentrations of tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-17 were measured in peripheral blood and serum of women with a history of RSA (N=40) compared with non-pregnant and fertile women as the control group (N=40) using quantitative real-time polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively.The mean age of patients and controls was 30.1 ± 4.28 and 30.03 ± 4.23, respectively. Patients had a history of at least 2 and at most 6 abortions. The mRNA levels of LIF were significantly lower in the women with RSA in comparison with the healthy participant (P=0.003). Regarding cytokine levels, no significant difference was seen between the two groups (P≥0.05). There was no correlation - between the LIF mRNA levels and TNF-α and IL-17 serum concentrations. The U-Mann-Whitney test and the Pearson correlation coefficient were applied to comparison variables between groups as well as a correlation between LIF mRNA and cytokine levels in serum.Despite a significant reduction in the LIF gene mRNA level in patients with RSA, it was not associated with increases in inflammatory cytokines. Dysfunction in the production of LIF protein may be involved in the onset of RSA disorder.
Etiology
Proinflammatory cytokine
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