Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With rising rates of alcohol consumption acute and chronic damage from alcohol is expected to increase all over the world. Habitual excessive alcohol consumption is associated with pathological effects on bone. The aim of the present in vitro study was to investigate comparatively the proliferation and synthetic activity of osteoblasts (OB) isolated from the trabecular bone of rats previously exposed to 7-week intermittent exposure to ethanol vapor, sham-aged rats and long-term estrogen deficient rats. Cell proliferation (WST1) and synthesis of alkaline phosphatase (ALP), osteocalcin (OC), collagen I (CICP), transforming growth factor beta1 (TGF-beta1), interleukin-6 (IL-6), tumor necrosis factor alfa (TNFalpha) were measured at 3, 7 and 14 days of culture. Osteoblast proliferation rate and TGF-beta1, IL-6 and TNFalpha syntheses were significantly affected by alcohol exposure. Estrogen deficiency and alcohol consumption share many common pathophysiological mechanisms of damage to bone, but alcohol affects OB proliferation and TNFalpha synthesis significantly more than menopause does. Therefore, these in vitro data suggest that alcohol has even more deleterious effects on bone than estrogen deficiency does.
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PMID:Intermittent exposure to ethanol vapor affects osteoblast behaviour more severely than estrogen deficiency does in vitro study on rat osteoblasts. 1759 Apr 96

Gastric ulcer is a multifaceted process including acid secretion, reactive oxygen species generation, prostaglandin inhibition, and extracellular matrix (ECM) degradation. Matrix metalloproteinases (MMPs) have the ability to cleave and remodel the ECM. We investigated the activity and expression of MMP-9 and -2 in ethanol-induced acute gastric ulceration in rats. We found that severity of gastric ulcer was strongly correlated with increasing doses of ethanol and increased secretion of proMMP-9. ProMMP-9 was upregulated approximately 25-fold at maximum ulcer index. Increased secretion of proMMP-9 was associated with increased expression of tumor necrosis factor-alpha and interleukin-6. We examined the effect of H(2)-receptor antagonists and antioxidants on proMMP-9 secretion and synthesis during prevention of ethanol-induced gastric ulcer. Our data reveal that famotidine dose dependently blocked increased secretion and synthesis of proMMP-9 during gastroprotection and arrested infiltration of inflammatory cells as well as oxidative stress in rat gastric tissues. Similar to H(2)-receptor antagonists, N-acetylcysteine and dimethyl sulfoxide, well-known antioxidants, inhibited proMMP-9 upregulation to the control level. In conclusion, ethanol-induced gastric ulceration is associated with increased expression of proMMP-9 that can be attenuated by H(2)-receptor antagonists and antioxidants. These findings furnish a novel MMP-9-mediated pathway and its inhibition via proinflammatory cytokines by famotidine in ethanol-induced gastric ulceration.
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PMID:Novel role of famotidine in downregulation of matrix metalloproteinase-9 during protection of ethanol-induced acute gastric ulcer. 1760 38

Chronic alcoholism complicated by alcoholic liver disease (ALD) is characterized by activation of inflammatory responses. Alcohol intake increases gut permeability allowing substances such as lipopolysaccharides (LPS) which are strong inducers of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) to enter the circulation. Vitamin C is an antioxidant with many cellular activities seemed to protect cells against alcohol-induced peroxidation. In present study, serum levels of TNF-alpha and IL-6 were measured by ELISA method in four groups of albino rats, each group consists of 10 rats. Group (I) was untreated group (control), group (II) was treated with ethanol, group (III) was treated with ascorbic acid and group (IV) was treated with ethanol + ascorbic acid. Results revealed that both TNF-alpha and IL-6 serum levels were very highly significantly increased in group (II) and (IV) than control group (1) (P < 0.001). Group (III) showed significantly (P < 0.001) decreased TNF-alpha serum level than group (II) and (IV) while it showed significantly (P < 0.001) increased IL-6 serum level than control group (I) and also significantly decreased IL-6 serum level than group (IV). Serum IL-6 level was significantly (P < 0.01) decreased in group (III) than (II). These results indicate that serum levels of the proinflammatory cytokines TNF-alpha and IL-6 may serve as predictive biomarkers for progression of ALD. In addition, using TNF-alpha neutralizing agent (or its antagonist)/or IL-6 as an anti-apoptotic factor could be useful as a treatment strategy of ALD.
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PMID:Effects of chronic ethanol and vitamin C administration on production of tumor necrosis factor-alpha and interleukin-6 in rats. 1797 45

Cardiovascular diseases are among the worldwide leading causes of shorter life expectancy and loss of quality of life. Thus, any influence of diet or life habits on the cardiovascular system may have important implications for public health. Most world populations consume alcoholic beverages. Since alcohol may have both protective and harmful effects on cardiovascular health, the identification of biochemical mechanisms that could explain such paradoxical effects is warranted. The vascular endothelium is the target of important mediating pathways of differential ethanol concentrations, such as oxidative stress, lipoproteins, and insulin resistance. Alcohol-induced endothelial damage or protection may be related to the synthesis or action of several markers, such as nitric oxide, cortisol, endothelin-1, adhesion molecules, tumor necrosis factor alpha, interleukin-6, C-reactive protein, and haemostatic factors. The expression of these markers is consistent with the J-shaped curve between alcohol consumption and cardiovascular health. However, there is genetic and phenotypic heterogeneity in alcohol response, and despite the apparent beneficial biochemical effects of low doses of ethanol, there is not enough clinical and epidemiological evidence to allow the recommendation to consume alcoholic beverages for abstemious individuals. Considering the potential for addiction of alcoholic beverage consumption and other negative consequences of alcohol, it would be worthwhile to identify substances able to mimic the beneficial effects of low doses of ethanol without its adverse effects.
Alcohol 2007 Nov
PMID:Alcohol consumption, cardiovascular health, and endothelial function markers. 1798 Jul 86

In vivo protective and alleviative effects of s-allyl cysteine (SAC), s-ethyl cysteine (SEC), s-methyl cysteine (SMC), and s-propyl cysteine (SPC) against alcohol-induced hepatotoxicity in Balb/cA mice were studied. In the preventive study, SAC, SEC, SMC, or SPC, each agent at 1 g/L, was added into the drinking water for 3 wk, and the mice were then treated with ethanol to induce acute liver injury. In the alleviative study, mice were first treated by ethanol followed by the 4 agent treatments for 3 wk. The preintake of these agents significantly attenuated subsequent alcohol-induced lipid oxidation, glutathione (GSH) depletion, and activity reduction of catalase and glutathione peroxidase (P < 0.05); also attenuated were the alcohol-induced elevation of c-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor (TNF)-alpha (P < 0.05). The preintake of these agents also significantly retarded alcohol-induced cytochrome P450 2E1 (CYP2E1) activity increase (P < 0.05). In the alleviative study, posttreatments from the 4 agents restored liver GSH content (P < 0.05); however, only SEC and SPC posttreatments significantly reduced lipid oxidation and alleviated the alcohol-induced elevation of CRP, IL-6, IL-10, and TNF-alpha (P < 0.05). SEC and SPC posttreatments also significantly diminished alcohol induced CYP2E1 activity (P < 0.05). These results support that SEC and SPC could provide both preventive and alleviative effects against alcohol-induced hepatotoxicity through suppression of oxidation and inflammation.
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PMID:Protective and alleviative effects from 4 cysteine-containing compounds on ethanol-induced acute liver injury through suppression of oxidation and inflammation. 1799 65

Chronic alcohol consumption is associated with pathological effects on bone, and it is correlated with the increasing risk of osteoporosis and fractures. The negative effects of alcohol intake also influence bone repair processes and the osseointegration of implants. The aim of the present in vitro study was to investigate the proliferation and synthetic activity of osteoblasts isolated from the trabecular bone of rats previously exposed to 7-week intermittent exposure to ethanol vapour (EE-OB), and sham-aged rats (SA-OB), when cultured on standard commercially pure Ti (cpTi). Osteoblast proliferation (WST-1), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I (CICP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) were measured at 1, 7, and 14 days of culture. Our results showed a decrease in the cell viability and synthetic activity of osteoblasts exposed to ethanol when cultured on cpTi. Moreover, the release of local regulatory factors from osteoblasts was imbalanced: TGF-beta1 production was reduced and TNF-alpha and IL-6 were up-regulated. These in vitro data suggest that alcohol abuse affects bone repair and decreases the ability to form bone around standard cpTi. Innovative surfaces and adjuvant therapies could be useful when implants are required in alcoholics.
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PMID:Chronic alcohol abuse and endosseous implants: linkage of in vitro osteoblast dysfunction to titanium osseointegration rate. 1799 4

Acute ethanol (EtOH) exposure causes a stress response in humans, nonhuman primates, and rodents. Previous study results indicate that the suppression of some immunological parameters by EtOH is mediated in part or completely by elevated corticosterone concentrations induced by EtOH. However, initial results suggested that corticosterone is not involved in the modulation of cytokine production by macrophages in response to polyinosinic polycytidylic acid (poly I:C). New studies were conducted to further evaluate the role of corticosterone in EtOH-mediated changes in production of interleukin-6 (IL-6), IL-10, and IL-12 in serum and peritoneal fluid in mice treated with poly I:C or lipopolysaccharide (LPS). Suppression of IL-6, but not IL-12, production by EtOH was found to be mediated by corticosterone. However, poly I:C, LPS, and EtOH all caused similar elevations of corticosterone concentrations; thus, it is not clear if EtOH is required to induce levels or durations of corticosterone needed to mediate the observed effects. The situation with IL-10 was more complicated. Inhibition of corticosterone synthesis with aminoglutethimide prevented the increase in IL-10 production caused by EtOH plus poly I:C as compared to poly I:C only. This indicates that this increase is dependent on corticosterone, but exogenous corticosterone plus poly I:C did not increase IL-10 production. Thus, EtOH and corticosterone are required. However, with LPS inhibition of corticosterone synthesis (using aminoglutethimide) or inhibition of its action (using mifepristone) further increased, or did not affect IL-10 concentrations, suggesting fundamental differences in the signaling pathways leading from poly I:C and LPS to IL-10 production.
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PMID:Role of corticosterone in immunosuppressive effects of acute ethanol exposure on Toll-like receptor mediated cytokine production. 1804 Aug 16

Hepatic cytochrome P450 (P450) enzymes are down-regulated during inflammation. In this study, an animal model of inflammatory bowel disease was subjected to characterization of hepatic P450 expression under inflammatory conditions. Rats were treated intracolonically with 100 mg/kg trinitrobenzene sulfonic acid (TNBS) dissolved in 30% ethanol, and homogenates of colonic mucosa and hepatic microsomes of the rats were prepared. The colitis was accompanied by appearance of higher levels of portal endotoxin, interleukin-6, and nitric oxide metabolites and decreases in contents and activities for hepatic CYP3A2, CYP2C11, and, to a lesser extent, CYP1A2 and CYP2E1. Nimesulide, a preferential COX-2 inhibitor, protected rats with TNBS-induced colitis (TNBS-colitis) against the down-regulation of hepatic CYP3A2. Polymyxin B, which neutralizes endotoxin, curcumin, which has anti-inflammatory properties, and gadolinium chloride, which inactivates macrophages, attenuated the down-regulation of CYP3A2. Similar effects were observed in other P450s such as CYP2C11, but the agents were less effective in attenuating the down-regulation. Our data suggest that endogenous substances leaked from damaged colon in the rats with TNBS-colitis activate Kupffer cells, leading to down-regulation of hepatic P450s with differential susceptibility to the inflammatory stimuli. The colitis model, instead of exogenous administration of lipopolysaccharide or cytokines, could be applied to the study on mechanisms for altered hepatic P450 expression and other liver functions under mild inflammatory conditions.
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PMID:Down-regulation of hepatic cytochrome P450 enzymes in rats with trinitrobenzene sulfonic acid-induced colitis. 1807 64

Alleviative effects of histidine and carnosine in mice against ethanol-induced oxidative and inflammatory was examined. After chronic alcoholic liver injury was induced, histidine and carnosine at 0.5, 1, 2g/L were added to the drinking water for 3 weeks. Results showed that the post-intake of histidine or carnosine markedly decreased alanine aminotransferase and aspartate aminotransferase activities (P<0.05). Ethanol treatment increased malondialdehyde (MDA) level, decreased glutathione (GSH) content and catalase and glutathione peroxidase (GPX) activities, and increased cytochrome P450 2E1 (CYP2E1) activity in liver (P<0.05). The post-intake of histidine and carnosine significantly decreased MDA formations, increased GSH content, enhanced catalase and GPX activities, and suppressed CYP2E1 activity (P<0.05), in which the effects on catalase and CYP2E1 activities were dose-dependent (P<0.05). Ethanol treatment elevated hepatic levels of c-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) (P<0.05), the post-intake of histidine and carnosine significantly and dose-dependently diminished the release of CRP, IL-6, and TNF-alpha (P<0.05). Ethanol treatment caused down-regulation in both catalase and GPX mRNA expression, and up-regulated both IL-6 and TNF-alpha mRNA expression (P<0.05). Histidine and carnosine post-treatments significantly and dose-dependently upregulated catalase mRNA, and down-regulated mRNA expression of IL-6 and TNF-alpha (P<0.05). Based on the observed anti-oxidative and anti-inflammatory effects, the supplement of histidine or carnosine might be helpful for the treatment of chronic alcoholic liver injury.
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PMID:Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. 1822 27

Hepatocyte apoptosis, inflammation, and fibrosis are prominent features of liver disease in general and of alcoholic liver injury in particular. Although the link between these processes remains unclear, one universal characteristic of liver injury is the induction of hepatocellular damage, which results in the generation of apoptotic bodies. Work from our laboratory over the last several years has studied the effect of ethanol administration on the process of apoptosis and a role for altered endocytosis in alcoholic apoptosis. We initially focused our research on the hepatocyte by examining endocytosis using the asialoglycoprotein receptor (ASGP-R) pathway as a model and we identified multiple ethanol-induced impairments in receptor function. We also showed that uptake of apoptotic bodies is impaired in hepatocytes isolated from ethanol-fed animals compared to controls, and that this impairment is linked to altered ASGP-R function. Recent work from our laboratory is examining a link between ethanol-impaired ASGP-R function, apoptotic body accumulation, and inflammation in the liver. We are particularly interested in data showing that factors produced by Kupffer cells incubated with apoptotic bodies can lead to production of tumor necrosis factor-alpha and interleukin-6, and that this effect is exacerbated in the setting of alcohol administration. In addition, we have preliminary data showing that media from Kupffer cell cultures incubated with apoptotic bodies can induce hepatocyte killing. The goal of our future work is to show that inadequate removal of apoptotic cells, in part via altered receptor-mediated endocytosis, plays a role in the course of pathogenesis of alcoholic liver injury.
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PMID:Impaired receptor-mediated endocytosis: its role in alcohol-induced apoptosis. 1833 63


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