Effects Of Interleukin-6 Research Articles

Inhibitory Effects of Hepatocyte Growth Factor and Interleukin-6 on Transforming Growth Factor-β1 Mediated Vocal Fold Fibroblast-Myofibroblast Differentiation

The role of myofibroblasts in vocal fold scarring has not been extensively studied, partly because of the lack of a robust in vitro model. The objective of this investigation was to develop and characterize a myofibroblast in vitro model that could be utilized to investigate the molecular mechanism of myofibroblast differentiation and function in injured vocal fold tissue. Differentiation of human primary vocal fold fibroblasts (hVFFs) to myofibroblasts was stimulated with 5, 10, or 20 ng/mL of recombinant transforming growth factor-beta1 (TGF-beta1). Cultures were analyzed by immunofluorescence and Western blotting, with an alpha-smooth muscle actin (alpha-SMA) antibody used as a myofibroblast marker. Normal rabbit vocal folds were treated with 10 ng/mL of TGF-beta1 for 7 days for in vivo corroboration. The effects of interleukin-6 (IL-6) and hepatocyte growth factor (HGF) on myofibroblast differentiation were studied with Western blots. The hVFFs demonstrated positive alpha-SMA labeling in cells stimulated by 10 and 20 ng/mL TGF-beta1, indicating that hVFFs were capable of differentiation to myofibroblasts. Transforming growth factor-beta1 induced the largest increase in alpha-SMA at 10 ng/mL on day 5 of treatment. Both HGF and IL-6 suppressed the expression of TGF-beta1-induced alpha-SMA. Our work characterizes a useful in vitro model of TGF-beta1-mediated vocal fold fibroblast-myofibroblast differentiation. The extent of differentiation appears to be attenuated by HGF, suggesting a potential mechanism to support prior work indicating that HGF plays a protective role in reducing scar formation in vocal fold injuries. Paradoxically, IL-6, which has been shown to play a profibrotic role in dermal studies, also attenuated the TGF-beta1 response.

Effect of interleukin-8 and RANTES on the Gardos channel activity in sickle human red blood cells: Role of the Duffy antigen receptor for chemokines

We investigated the effects of the chemokines IL-8 and RANTES on the activity of the Gardos channel (GC) of sickle red blood cells (SSRBCs). SSRBCs expressing the Duffy antigen receptor for chemokines (DARC) incubated under oxygenated conditions exhibit GC activation. The deoxygenation-stimulated K + loss via the GC is activated by the chemokines in the Duffy-positive SSRBCs. The percentage of cells with high density is 17 times higher in the Duffy-positive group. These findings are consistent with a greater susceptibility of Duffy-positive SSRBCs to inflammatory chemokines leading to GC activation and cellular dehydration and suggest a coupling, promoted by the sickling process, between DARC and the GC.

Blockade of interleukin 1 in type 1 diabetes mellitus

Interleukin 1 (IL-1) is a 17 kDa protein highly conserved through evolution and is a key mediator of inflammation, fever and the acute-phase response. IL-1 has important functions in the innate immune defense against microbes, trauma and stress, and is also an effector molecule involved in tissue destruction and fibrosis. The inhibition of IL-1 action has clinical efficacy in many inflammatory diseases, such as hereditary autoinflammatory disorders, familial hereditary fever, gout, rheumatoid arthritis and type 2 diabetes mellitus (T2DM). The latter is a common metabolic condition caused by insulin resistance and pancreatic beta-cell failure, the causes of both of which have inflammatory components. IL-1 signaling has roles in beta-cell dysfunction and destruction via the NFkappaB and mitogen-activated-protein-kinase pathways, leading to endoplasmic reticulum and mitochondrial stress and eventually activating the apoptotic machinery. In addition, IL-1 acts on T-lymphocyte regulation. The modulating effect of IL-1 on the interaction between the innate and adaptive immune systems and the effects of IL-1 on the beta-cell point to this molecule being a potential interventional target in autoimmune diabetes mellitus. Genetic or pharmacological abrogation of IL-1 action reduces disease incidence in animal models of type 1 diabetes mellitus (T1DM) and clinical trials have been started to study the feasibility, safety and efficacy of IL-1 therapy in patients with T1DM. Here, we review the rationale for blocking IL-1 in patients with T1DM.

Cell-associated interleukin 1 production of alveolar macrophages from bleomycin-induced pulmonary fibrosis in rats

In order to clarify the mechanisms of pulmonary fibrosis, we produced bleomycin (BLM)-induced pulmonary fibrosis in rats and examined the ability of alveolar macrophages (AM) to produce interleukin-1 (IL-1). BLM (0.9 mg) was administered once via the trachea to male Wistar rats weighing about 200 g. Bronchoalveolar lavage was performed at 1, 3, 6, 9 and 12 days after administration. AM were incubated for 24 hours, then extracellular IL-1 in the supernatants and cell-associated IL-1 of AM were measured by proliferation assay of mouse thymocytes. Cell-associated IL-1 activity was measured after fixation by paraformaldehyde (PFA). Extracellular IL-1 was detected in the culture media of AM at only day 1 after administration. On the other hand, cell-associated IL-1 was detected in AM fixed by PFA on days 1, 3, 6 and 9 after administration. AM from BLM-induced pulmonary fibrosis in rats were fixed by PFA and then were treated with anti-IL-1 alpha antibody or anti-IL-1 beta antibody. Cell-associated IL-1 activity was neutralized by treatment with anti-IL-1 alpha antibody and was not neutralized by treatment with anti-IL-1 beta antibody. Following this, the effect of cell-associated IL-1 on pulmonary fibroblasts was examined. This was estimated by the proliferation of pulmonary fibroblasts using incorporation of 3H-thymidine. When pulmonary fibroblasts were incubated with AM fixed by PFA from BLM-induced pulmonary fibrosis in rats, proliferation of pulmonary fibroblasts was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1

Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions. Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4h/day at 1 Hz and 0%-26% strain for 14 days in the presence of 0 or 100 pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed. IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair. Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions.

Effects of Interleukin-6 on Depression Risk in Dialysis Patients

Background/Aims: Depression represents the most frequent psychiatric disorder in nephrology. Cytokines, and especially IL-6, were found to be elevated in depressed patients with normal renal function. The objective of this pilot study was to examine the relationship between depression and cytokines (IL-6, TNF-α, and IL-10) in patients with end-stage kidney disease (ESKD). Methods: We studied 44 stable patients with ESKD for 71 ± 66 months (32 males; 64 ± 13 years; 27 on hemodialysis and 17 on peritoneal dialysis). The control group included 20 healthy age- and gender-matched individuals (12 males; 60 ± 12 years). Depression was assessed by the Zung Self-Rating Depression Scale (ZS). Nephelometry for high-sensitivity CRP and ELISA kits for IL-6, IL-10 and TNF-α were used. Results: Compared to controls, patients with ESKD had higher ZS scores (56.8 ± 16.8 vs. 44 ± 12.7, p < 0.01), WBC (7,987 ± 2,347 vs. 6,413 ± 870/mm³, p < 0.01), ESR (36.3 ± 15.8 vs. 9.4 ± 3.3 mm, p < 0.001), TNF-α (52 ± 18.4 vs. 10.7 ± 2.8 pg/ml, p < 0.001) and IL-6 (6.3 ± 4 vs. 1.8 ± 0.4 pg/ml, p < 0.001). No differences in high-sensitivity CRP and IL-10 were noted between the ESKD and control groups. Serum IL-6 levels were the only parameter positively correlated with the values of the ZS score in ESKD patients (r = 0.34, p < 0.02). Conclusions: IL-6 may play a role in the pathogenesis of depression in patients with ESKD.

Expression of interleukin-1 (IL-1) ligands system in the most common endometriosis-associated ovarian cancer subtypes

ObjectivesEndometrioid carcinoma of the ovary is one of the most types of epithelial ovarian cancer associated to endometrioisis. Endometrioid tumors as well as endometriotic implants are characterized by the presence of epithelial cells, stromal cells, or a combination of booth, that resemble the endometrial cells, suggesting a possible endometrial origin of these tumors. Pro-inflammatory cytokines, including interleukin-1 (IL-1) have been reported to be involved in both endometriosis and ovarian carcinogenesis. The major objective of this study was to determine the level expression of IL-1 ligands system (IL-1α, IL-1β and IL-1RA) in the most common subtypes of ovarian cancer cells compared to endometrial cells.MethodsWe used primary endometrial cells, endometrial cell line RL-952 and different subtypes of epithelial ovarian cancer cell lines including TOV-112D (endometrioid), TOV-21G (clear cell) and OV-90 (serous). Immunofluorescence and real-time PCR analysis were used respectively for detecting IL-1 ligands at the levels of cell-associated protein and mRNA. Soluble IL-1 ligands were analyzed by ELISA.ResultsWe demonstrated that IL-1 ligands were expressed by all endometriosis-associated ovarian cancer subtypes and endometrial cells. In contrast to other cancer ovarian cells, endometrioid cells exhibit a specific decrease of cell-associated IL-1RA expression and its soluble secretion.ConclusionEndometrioid ovarian cancer exhibits an alteration in the expression of IL-1RA, a key protector against tumorogenic effects of IL-1. This alteration evokes the same alteration observed in endometriotic cells in previous studies. This suggests a possible link between the endometrium, the tissue ectopic endometriosis and endometrioid ovarian cancer.

Dual Roles for Perivascular Macrophages in Immune-to-Brain Signaling

Cytokines produced during infection/inflammation activate adaptive central nervous system (CNS) responses, including acute stress responses mediated by the hypothalamo-pituitary-adrenal (HPA) axis. The mechanisms by which cytokines engage HPA control circuitry remain unclear, though stimulated release of prostanoids from neighboring vascular cells has been implicated in this regard. How specific vascular cell types, endothelial cells (ECs) versus perivascular cells (PVCs; a subset of brain-resident macrophages), participate in this response remains unsettled. We exploited the phagocytic activity of PVCs to deplete them in rats by central injection of a liposome-encapsulated proapoptotic drug. This manipulation abrogated CNS and hormonal indices of HPA activation under immune challenge conditions (interleukin-1) that activated prostanoid synthesis only in PVCs, while enhancing these responses to stimuli (lipopolysaccharide) that engaged prostanoid production by ECs as well. Thus, PVCs provide both prostanoid-mediated drive to the HPA axis and an anti-inflammatory action that constrains endothelial and overall CNS responses to inflammatory insults.

ウシ顆粒層細胞のステロイド産生におけるインターロイキン-8(IL-8)の作用

ウシ顆粒層細胞のステロイド産生におけるインターロイキン-8(IL-8)の作用

Interleukin 1 regulates its own receptors in human endometrial cells via distinct mechanisms

Interleukin 1 (IL1) plays an important role in the physiology of human endometrium and is recognized as a major and early embryonic signal. Tight control over the local endometrial action of this cytokine is critical for normal reproductive functions. The coordinated regulation of IL1 receptors types I and II (IL1R1 and IL1R2) and IL1 receptor antagonist (IL1RA) in endometrial cells may represent one of the principle mechanisms involved in the control of IL1 local effects. The objective of this study was to investigate the regulation of IL1Rs in human endometrial epithelial cells in response to IL1. Cultures of KLE endometrial epithelial cell line and primary human endometrial epithelial cells, immunofluorescent staining, enzyme-linked immunosorbent assay, western blotting, nuclear transcription (run-on) and real-time PCR were used to investigate the expression of IL1R1, IL1R2 and IL1RA. Cells appeared to react to IL1 by up-regulating the expression of the signaling activating IL1R1 and to moderate in parallel IL1 effects by elevating the expression of the decoy inhibitory IL1R2 and the receptor antagonist IL1RA. Regulation of IL1R1 and IL1RA by IL1B involved gene transcription activation and that of IL1R2 involved mRNA stabilization. Considering IL1's immunomodulatory, proangiogenic and tissue remodeling properties, and its role as an embryonic signal, modulation of endometrial cell responsiveness to IL1 via the concomitant regulation of its own activating and inhibitory receptors and receptor antagonist may represent an important regulatory mechanism of IL1-induced physiological changes occurring in the human endometrium during the normal menstrual cycle and embryo development.

A stable isotope method for the simultaneous measurement of matrix synthesis and cell proliferation in articular cartilage in vivo

Measurements of cell proliferation and matrix synthesis in cartilage explants have identified regulatory factors [e.g., interleukin-1 (IL-1)] that contribute to osteoarthritis and anabolic mediators [e.g., bone morphogenic protein-7 (BMP-7)] that may have therapeutic potential. The objective of this study was to develop a robust method for measuring cell proliferation and glycosaminoglycan synthesis in articular cartilage that could be applied in vivo. A stable isotope-mass spectrometry approach was validated by measuring the metabolic effects of IL-1 and BMP-7 in cultures of mature and immature bovine cartilage explants. The method was also applied in vivo to quantify physiologic turnover rates of matrix and cells in the articular cartilage of normal rats. Heavy water was administered to explants in the culture medium and to rats via drinking water, and cartilage was analyzed for labeling of chondroitin sulfate (CS), hyaluronic acid (HA) and DNA. As expected, IL-1 inhibited the synthesis of DNA and CS in cartilage explants. However, IL-1 inhibited HA synthesis only in immature cartilage. Furthermore, BMP-7 was generally stimulatory, but immature cartilage was significantly more responsive than mature cartilage, particularly in terms of HA and DNA synthesis. In vivo, labeling of CS and DNA in normal rats for up to a year indicated half-lives of 22 and 862 days, respectively, in the joint. We describe a method by which deuterium from heavy water is traced into multiple metabolites from a single cartilage specimen to profile its metabolic activity. This method was demonstrated in tissue culture and rodents but may have significant clinical applications.

The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis.

BackgroundMany cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.MethodsExperiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2nd to 5th passage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca2+]i), cell contraction, migration and proliferation.ResultsThe IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca2+ release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC20) in CF than in control cells. In addition, MLC20 expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.ConclusionASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC20. Higher expression of MLC20 by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.

Physiologic deformational loading does not counteract the catabolic effects of interleukin-1 in long-term culture of chondrocyte-seeded agarose constructs

An interplay of mechanical and chemical factors is integral to cartilage maintenance and/or degeneration. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that is present at elevated concentrations in osteoarthritic joints and initiates the rapid degradation of cartilage when cultured in vitro. Several short-term studies have suggested that applied dynamic deformational loading may have a protective effect against the catabolic actions of IL-1. In the current study, we examine whether the long-term (42 days) application of dynamic deformational loading on chondrocyte-seeded agarose constructs can mitigate these catabolic effects. Three studies were carried out using two IL-1 isoforms (IL-1 α and IL-1 β) in chemically defined medium supplemented with a broad range of cytokine concentrations and durations. Physiologic loading was unable to counteract the long-term catabolic effects of IL-1 under any of the conditions tested, and in some cases led to further degeneration over unloaded controls.

Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls

We assessed the main and interaction effects of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. A total of 228 premenarche Chinese girls (9-11.5 years old) were recruited for a 2-year follow-up study. Bone mineral density (BMD) at the total body, lumbar spine (L1-L4), and total left hip were measured by dual-energy X-ray absorptiometry at baseline and follow-up. The -174G/C and -634C/G polymorphism of IL-6 gene, and PvuII and XbaI polymorphisms of the estrogen receptor (ER)-alpha gene, were determined. The -634C/G polymorphism of the IL-6 gene and PvuII polymorphism of ER-alpha gene were significantly associated with bone mass accrual after adjusting the potential confounding factors. Girls with pp genotype of ER-alpha gene had greater percentage accrual in BMD of total body (P = 0.010) and femoral intertrochanter (P = 0.038) than their PP and Pp counterparts. Girls with CC genotype of IL-6 -634G/C gene had higher percentage accrual in BMD of total body (P = 0.032) and femoral trochanter (P = 0.048) than their CG + GG counterparts. Significant interaction effects of IL-6 -634C/G polymorphism and ER-alpha PvuII polymorphism were observed on percentage change in BMD of total left hip (P = 0.009) and femoral intertrochanter (P = 0.007). The genotype CC (IL-6 -634C/G) x pp (ER-alpha PvuII) was associated with greater BMD accrual than other genotype combination in Chinese adolescent girls. We found that the IL-6 -634C/G and ER-alpha PvuII polymorphism were significantly associated with BMD accrual and that they have an interactional effect on BMD accrual in Chinese adolescent girls.

Suppression of DNA-PK effected the radiosensitivity and cell cycle of HeLa

Interleukin 1 (IL-1) is a pleiotropic cytokine able to induce cytocidal effect. The aim of the presented work was to analyze the mechanism of IL-1-induced cytocidal effect in HeLa cells in the presence of cycloheximide (CHX). We found that the pattern of IL-1-induced cell death shares significant similarities with the effect of tumor necrosis factor (TNF) in these cells. Subsequently, we identified IL-1 cytotoxicity as an indirect effect. The supernatant collected from the cells treated with IL-1 and CHX showed toxic activity towards IL-1-resistant while TNF-sensitive A9 cells. Furthermore, antibodies neutralizing TNF blocked HeLa cell death induced by IL-1/CHX. TNF was then detected in HeLa cells by means of flow cytometry, fluorescence microscopy and ELISA of detergent-soluble cell extracts. In the presence of an inhibitor of TNF sheddase (TACE), the cytotoxic effect of IL-1/CHX and the amount of TNF protein in detergent-soluble cell extracts were enhanced. These results suggest that in response to interleukin 1/CHX, the amount of transmembrane TNF is increased. Taken together, we demonstrated that the mechanism of IL-1 cytotoxic activity in HeLa cells in the presence of CHX depends on the function of soluble and transmembrane TNF.

The effects of interleukin-6 on the contraction and relaxation responses of the cavernous smooth muscle from rats

The purpose of this study is to elucidate the effect of IL-6 on the vasomotor reactivity of the corpus cavernosum of the rats. The strips were either left untreated or treated with 1 ng/ml of IL-6 for 60 min. By increasing concentrations of phenylephrine, acetylcholine, or sodium nitroprusside, we assessed concentration–contraction or relaxation responses. The IL-6-treated strips were incubated for 30 min with or without l-NAME (NW-nitro-l-arginine methyl ester), l-arginine, indomethacin, BQ-123 (an endothelin receptor A inhibitor), or SQ 29,548 (a thromboxane A2 [TXA2] receptor blocker), and the effects on phenylephrine-induced contraction or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. The contractile responses to phenylephrine were significantly enhanced in the IL-6-treated strips, compared with the IL-6-nontreated strips, and the relaxation responses to acetylcholine were significantly inhibited in the IL-6-treated group compared with the IL-6-nontreated group. But after endothelial denudation, there was no difference between the IL-6-treated strips and the IL-6-nontreated strips on the contraction–relaxation responses to phenylephrine or acetylcholine. The relaxation responses to sodium nitroprusside were not inhibited in both groups. l-NAME completely inhibited the relaxation response to acetylcholine in the IL-6-treated strips, as well as the IL-6-nontreated strips. Indomethacin and SQ 29,548 significantly inhibited the increased contractile responses to phenylephrine in the IL-6-treated strips. But BQ 123 rarely affected the same responses. l-arginine reversed the inhibited relaxation responses to acetylcholine in the IL-6-treated strips. Therefore, IL-6 inhibits endothelium-dependent, NO-mediated relaxation and also enhances α1-adrenergic receptor-mediated contraction via an endothelium-dependent TXA2-mediated mechanism in the corpus cavernosum of the rat.

Cytocidal effect of interleukin 1 (IL-1) on HeLa cells is mediated by both soluble and transmembrane tumor necrosis factor (TNF)

Interleukin 1 (IL-1) is a pleiotropic cytokine able to induce cytocidal effect. The aim of the presented work was to analyze the mechanism of IL-1-induced cytocidal effect in HeLa cells in the presence of cycloheximide (CHX). We found that the pattern of IL-1-induced cell death shares significant similarities with the effect of tumor necrosis factor (TNF) in these cells. Subsequently, we identified IL-1 cytotoxicity as an indirect effect. The supernatant collected from the cells treated with IL-1 and CHX showed toxic activity towards IL-1-resistant while TNF-sensitive A9 cells. Furthermore, antibodies neutralizing TNF blocked HeLa cell death induced by IL-1/CHX. TNF was then detected in HeLa cells by means of flow cytometry, fluorescence microscopy and ELISA of detergent-soluble cell extracts. In the presence of an inhibitor of TNF sheddase (TACE), the cytotoxic effect of IL-1/CHX and the amount of TNF protein in detergent-soluble cell extracts were enhanced. These results suggest that in response to interleukin 1/CHX, the amount of transmembrane TNF is increased. Taken together, we demonstrated that the mechanism of IL-1 cytotoxic activity in HeLa cells in the presence of CHX depends on the function of soluble and transmembrane TNF.

Effects of interleukin-6 −174C/G and metallothionein 1A +647A/C single-nucleotide polymorphisms on zinc-regulated gene expression in ageing

Decreased zinc ion availability in ageing is associated with altered immune response. One of the main regulators of zinc availability is metallothionein. Metallothionein induction is under the control of interleukin-6, a pro-inflammatory cytokine whose production is associated with poor ageing. The production of interleukin-6 is controlled, in part, by variability in the −174 nucleotide position. Under conditions of chronic inflammation, such as in ageing, zinc release by metallothionein is limited and may reduce zinc availability. Understanding the precise nature of the interactions between interleukin-6 and metallothioneins will aid in identifying individuals who are at risk of zinc deficiency. In the current study, we used gene arrays to investigate the effects of in vitro zinc supplementation on gene expression in elderly donors with described interleukin-6 and metallothionein 1a polymorphisms. Ingenuity Pathway Analysis™ identified several zinc-responsive genetic networks uniquely regulated only in elderly individuals with the pro-inflammatory interleukin-6 polymorphism. These include zinc-dependent decreased transcription of pro-inflammatory cytokines and alterations in metabolic regulatory pathways. The genomic effects of zinc increased in significance in the presence of the metallothionein 1a +647 C/A transition, suggesting that the interleukin-6 and metallothionein 1a genes act in a concerted manner to control zinc-regulated gene expression.

Comparison of serum levels of inflammatory markers and allelic variant of interleukin-6 in patients with acute coronary syndrome and stable angina pectoris

Although the relationship between atherosclerosis and inflammatory cells has been recognized in recent years, the effect of interleukin-6 (IL-6) genetic variants associated with atherosclerosis is still controversial. Therefore, we investigated the association between IL-6 polymorphism and levels of IL-6 in patients with coronary artery disease (CAD). We conducted a case-control study on 294 unrelated participants who were referred to the cardiology department of the university hospital for coronary angiography because of suspected ischemic heart disease. Group I comprised patients with clinically acute coronary syndrome, and group II comprised patients (individuals matched for age and sex) with clinically stable angina pectoris; both groups were categorized, based on their angiographic findings, as either having angiographically documented less extensive CAD (1 vessel narrowed) or extensive CAD (> or =2 vessels narrowed). They were studied to examine effect of the IL-6 gene variants in CAD. Genotyping was determined by polymerase chain reaction. The IL-6 G/C-174 polymorphism was found in 19 of 106 (18%) in group I and in four of 188 (2%) in group II (P<0.001). Median IL-6 levels were significantly higher in group I (6.7+/-13.6 pg/ml) than in group II (4.1+/-3.8 pg/ml) (P<0.05). In addition, high sensitivity C-reactive protein levels were significantly higher in group I (8.2+/-6.2 mg/dl) than in group II (4.6+/-3.4 mg/dl) (P<0.001). These results demonstrated that the presence of the IL-6 G/C-174 polymorphism and increased IL-6 and high sensitivity C-reactive protein levels are strongly associated with the inflammatory system and the course of clinical and hemodynamically significant CAD.

Effects of interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor on the proliferation and differentiation of adult human myoblasts.

Our previous studies have demonstrated that ciliary neurotrophic factor, a member of the interleukin-6-type cytokine superfamily, could inhibit the differentiation of myoblasts into mature myotubes at a certain concentration. In this study, another two members, interleukin-6 and leukemia inhibitory factor, together with ciliary neurotrophic factor were tested their roles in the proliferation and differentiation of myoblasts derived from the adult human skeletal muscles, in order to confirm that these cytokines might be a new type of regulatory factors on the myoblasts. The results showed that the effects of interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor on the proliferation and differentiation of adult human myoblasts were different. Leukemia inhibitory factor in the dose of 10 ng/ml could accelerate the cell proliferation. Leukemia inhibitory factor in the dose of 10 or 50 ng/ml and ciliary neurotrophic factor in the dose of 10 or 50 ng/ml could inhibit the myoblast differentiation. The inhibition mechanism might be that leukemia inhibitory factor and ciliary neurotrophic factor inhibited the expressions of transcription factor MyoD/myf5, which could regulate the myoblast differentiation. This study will provide the experimental and theoretic foundations for the basic and clinical researches about human myoblasts.