IL-6 Protein Expression Levels Research Articles

Effects of overexpression of human tissue inhibitor of metalloproteinase-1 on the inflammatory response in rats with myocardial infarction and related mechanisms

Objective: To observe the effects of recombinant adenovirus with human tissue inhibitor of metalloproteinase-1(Ad-hTIMP-1) on the inflammatory response in rats with myocardial infarction (MI) and explore the related mechanisms. Methods: The male Wistar rats were randomly divided into sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group according to the random number table (n=8 each group). MI was induced by ligation of the left anterior descending coronary artery and MI rats were injected with saline, Ad-Track and Ad-hTIMP-1, respectively. Sham-operated rats received similar surgical procedure without ligation of the left anterior descending coronary artery. After 4 weeks, the cardiac function was measured by echocardiography, then rats were sacrificed and hearts were removed for morphological and biological analysis. The morphology of myocardial tissue in each group was detected by HE staining and Masson staining. The mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and C-reactive protein(CRP) were detected by real-time PCR. Immune histochemical staining was performed to observe the protein expression levels of IL-6 and CRP. Results: (1) Left ventricular end systolic dimension derived from echocardiography was increased in saline group ((5.10±0.72) mm) and Ad-Track group ((4.88±0.64) mm) compared to sham-operated group ((4.25±0.46) mm), which was reduced in Ad-hTIMP-1 group ((4.13±0.35) mm, all P<0.05). The left ventricular ejection fraction was (72.46±5.74)%, (64.27±8.52)%, (64.65±3.90)%, and (71.55±6.95)%, the fractional shortening was (36.90±4.97)%, (29.03±3.40)%, (30.95±2.51)%, and (36.31±5.68)% in sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group, respectively. The left ventricular ejection fraction and fractional shortening in saline group and Ad-Track group were lower than those in sham-operated group and Ad-hTIMP-1 group (all P<0.05). (2) Necrosis of myocardial cells was not found and a small amount of immune cell infiltration and interstitial fibrosis were observed on HE and Masson stained myocardial sections of Ad-hTIMP-1 group. (3) Real-time PCR showed that mRNA expressions of TNF-α, IL-6, IL-10 and CRP were lower in Ad-hTIMP-1 group than in saline group. mRNA expressions of TNF-α, IL-10 and CRP were lower in Ad-hTIMP-1 group than in Ad-Track group (all P<0.05). (4) Immune histochemical staining showed that protein expressions of IL-6 and CRP were higher in saline group and Ad-Track group than those in Ad-hTIMP-1 group (all P<0.05). Conclusion: Recombinant adenovirus Ad-hTIMP-1 can improve cardiac function in rats with myocardial infarction via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-6 and CRP.

Red pitaya juice supplementation ameliorates energy balance homeostasis by modulating obesity-related genes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats.

BackgroundRed pitaya (Hylocereus polyrhizus) or known as buah naga merah in Malay belongs to the cactus family, Cactaceae. Red pitaya has been shown to give protection against liver damage and may reduce the stiffness of the heart. Besides, the beneficial effects of red pitaya against obesity have been reported; however, the mechanism of this protection is not clear. Therefore, in the present study, we have investigated the red pitaya-targeted genes in obesity using high-carbohydrate, high-fat diet-induced metabolic syndrome rat model.MethodsA total of four groups were tested: corn-starch (CS), corn-starch + red pitaya juice (CRP), high-carbohydrate, high-fat (HCHF) and high-carbohydrate, high-fat + red pitaya juice (HRP). The intervention with 5 % red pitaya juice was continued for 8 weeks after 8 weeks initiation of the diet. Retroperitoneal, epididymal and omental fat pads were collected and weighed. Plasma concentration of IL-6 and TNF-α were measured using commercial kits. Gene expression analysis was conducted using RNA extracted from liver samples. A total of eighty-four genes related to obesity were analyzed using PCR array.ResultsThe rats fed HCHF-diet for 16 weeks increased body weight, developed excess abdominal fat deposition and down-regulated the expression level of IL-1α, IL-1r1, and Cntfr as compared to the control group. Supplementation of red pitaya juice for 8 weeks increased omental and epididymal fat but no change in retroperitoneal fat was observed. Red pitaya juice reversed the changes in energy balance homeostasis in liver tissues by regulation of the expression levels of Pomc and Insr. The increased protein expression levels of IL-6 and TNF-α in HCHF group and red pitaya treated rats confirmed the results of gene expression.ConclusionCollectively, this study revealed the usefulness of this diet-induced rat model and the beneficial effects of red pitaya on energy balance homeostasis by modulating the anorectic, orexigenic and energy expenditure related genes.

Diesel Exhaust Particles Upregulate Interleukins IL-6 and IL-8 in Nasal Fibroblasts.

BackgroundDiesel exhaust particles (DEP) are a major source of air pollution. Nasal fibroblasts are known to produce various cytokines and chemokines. The aim of this study was to evaluate DEP-induced cytokines and chemokines in nasal fibroblasts and to identify the signaling pathway involved.MethodsA cytokine and chemokine array performed after stimulation of nasal fibroblasts with DEP revealed that levels of IL-6 and IL-8 were increased most significantly among various cytokines and chemokines. RT—PCR and ELISA were used to determine the mRNA and protein expression levels of IL-6 and IL-8. Signaling pathways of p-38, Akt, and NF-κB were analyzed by western blotting, luciferase assay, and ELISA. Organ cultures of nasal interior turbinate were also developed to demonstrate the ex vivo effect of DEP on the expression of IL-6 and IL-8 and the associated signaling pathway.ResultsDEP increased the expressions of IL-6 and IL-8 in nasal fibroblasts at mRNA and protein levels. DEP induced phosphorylation of p38, Akt, and NF-κB, whereas inhibitors of p38, Akt, and NF-κB blocked these phophorylations and the expressions of IL-6 and IL-8. These findings were also observed in ex vivo organ culture of nasal inferior turbinate.ConclusionsDEP induces expression of IL-6 and IL-8 via p38, Akt, and NF-κB signaling pathways in nasal fibroblasts. This finding suggests that air pollution might induce or aggravate allergic rhinitis or chronic rhinosinusitis.

Shuangtengbitong tincture treatment of collagen-induced arthritis via downregulation of the expression of IL-6, IL-8, TNF-α and NF-κB

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease and may lead to joint damage, synovial membrane destruction and cartilage and bone damage. RA is closely associated with increased expression of interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) and nuclear transcription factor-κB (NF-κB). Therefore, inhibition of the expression of IL-6, IL-8, TNF-α and NF-κB is a promising strategy for the development of novel anti-RA therapies. The aim of this study was to investigate the effect of shuangtengbitong tincture (STBT) on the expression of IL-6, IL-8, TNF-α and NF-κB in synovial tissues of rats with collagen-induced arthritis (CIA). STBT as a clinical prescription created at Fujian University of Traditional Chinese Medicines (TCM) Affiliated People’s Hospital has been shown to be clinically effective in the treatment of RA. The model of Wistar rats with CIA was created using bovine type II collagen. The two treatment groups with CIA were administered STBT (1 ml per time) or Votalin (∼1 cm per time) for ∼1 month continuously. Following treatment, STBT suppressed paw swelling significantly (P<0.05) compared with the model group. STBT also improved pathological changes, STBT-treated rats showed a significant improvement in synovial hyperplasia, inflammatory infiltration, cartilage and bone destruction and other symptoms. The protein expression levels of IL-6, IL-8, TNF-α and NF-κB were markedly suppressed in synovial tissues of STBT-treated and Votalin-treated rats. Our findings demonstrate for the first time that STBT markedly reduces paw swelling, improves pathological changes and increases the expression of IL-6, IL-8, TNF-α and NF-κB in synovial tissues of CIA rats, which may partially explain the anti-RA activity of STBT.

5′‐N‐ethylcarboxamide induces IL‐6 expression via MAPKs and NF‐κB activation through Akt, Ca2+/PKC, cAMP signaling pathways in mouse embryonic stem cells

Many studies suggest that adenosine modulates cell responses in a wide array of tissues through potent and selective regulation of cytokine production. This study examined the effects of adenosine on interleukin (IL)-6 expression and its related signal pathways in mouse embryonic stem (ES) cells. In this study, the adenosine analogue 5'-N-ethylcarboxamide (NECA) increased IL-6 protein expression level. Mouse ES cells expressed the A(1), A(2A), A(2B), and A(3) adenosine receptors (ARs), whose expression levels were increased by NECA and NECA-induced increase of IL-6 mRNA expression or secretion level was inhibited by the non-specific AR inhibitor, caffeine. NECA increased Akt and protein kinase C (PKC) phosphorylation, intracellular Ca(2+) and cyclic adenosine monophosphate (cAMP) levels, which were blocked by caffeine. On the other hand, NECA-induced IL-6 secretion was partially inhibited by Akt inhibitor, bisindolylmaleimide I (PKC inhibitor), SQ 22536 (adenylate cyclate inhibitor) and completely blocked by the 3 inhibitor combination treatment. In addition, NECA increased mitogen activated protein kinase' (MAPK) phosphorylation, which were partially inhibited by the Akt inhibitor, bisindolylmaleimide I, and SQ 22536 and completely blocked by the 3 inhibitor combination treatment. NECA-induced increases of IL-6 protein expression and secretion levels were inhibited by MAPK inhibition. NECA-induced increase of nuclear factor (NF)-kappaB phosphorylation was inhibited by MAPK inhibitors. NECA also increased cAMP response element-binding protein (CREB) phosphorylation, which was blocked by MAPK or NF-kappaB inhibitors. Indeed, NECA-induced increase of IL-6 protein expression and secretion was blocked by NF-kappaB inhibitors. In conclusion, NECA stimulated IL-6 expression via MAPK and NF-kappaB activation through Akt, Ca(2+)/PKC, and cAMP signaling pathways in mouse ES cells. J. Cell. Physiol. 219: 752-759, 2009. (c) 2009 Wiley-Liss, Inc.