Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-8 is a neutrophil chemoattractant that has been implicated in the pathogenesis of alcoholic hepatitis. The mechanism of ethanol-induced interleukin-8 production in liver is uncertain, although hepatocytes and Kupffer cells have both been proposed as sources of the chemokine. In this study we investigated whether short-term ethanol exposure stimulates production of rat interleukin-8 [cytokine-induced neutrophil chemoattractant (CINC)] by normal rat hepatocytes and Kupffer cells in primary culture. Initial experiments verified that hepatocytes and Kupffer cells produce CINC in response to cytokines or lipopolysaccharide. Ethanol, by contrast, failed to stimulate CINC secretion by either cell type even at concentrations as high as 100 mM. Although ethanol had no direct effect on liver cell CINC production, conditioned medium from ethanol-treated hepatocytes induced a threefold rise in CINC production by Kupffer cells. The increase was abrogated when hepatocytes were treated with ethanol and the metabolic inhibitor 4-methylpyrazole. The results suggest that the mechanism of ethanol-induced CINC production is indirect, involving ethanol oxidation and communication between hepatocytes and Kupffer cells.
 ...
PMID:Rat hepatocytes and Kupffer cells interact to produce interleukin-8 (CINC) in the setting of ethanol. 748 3

Interleukin-8 (IL-8), an inflammatory cytokine that promotes neutrophil accumulation, has been implicated in the pathogenesis of alcoholic liver disease but the mechanism of its production is unknown. The ability of lipid peroxidation products, also implicated in alcoholic liver disease, to stimulate IL-8 production was studied because of their alleged role in alcoholic liver disease. Peroxidized fatty acids (arachidonic and linolenic) as well as microsomal membranes stimulated IL-8 production by peripheral blood monocytes whereas ethanol and acetaldehyde did not. Hydrocortisone (5 microg/ml) prevented the IL-8 stimulation by peroxidized fatty acids. Ethanol-induced lipid peroxidation may secondarily further alcohol-induced liver injury through IL-8 chemotaxis of neutrophils.
 ...
PMID:Stimulation of monocyte interleukin-8 by lipid peroxidation products: a mechanism for alcohol-induced liver injury. 966 13

Evidence suggests a link between alcohol consumption, psoriasis and the response of psoriatic patients to methotrexate (MTX) therapy. Ethanol (EtOH) may play a role in the pathogenesis of psoriasis by upregulating the expression and inducing the local secretion of proinflammatory cytokines, e.g. interleukins IL-1alpha, IL-6, chemokine IL-8 and tumor necrosis factor alpha (TNF-alpha). We investigated whether EtOH or MTX or their combination influence the secretion of these cytokines using normal human primary skin cells (NHPSC) and epidermoid cell line A431. The objectives of this study were: (1) to quantify the differences in cellular changes induced by MTX, (2) to measure the effect of EtOH on MTX toxicity and (3) to determine the relationship between MTX and EtOH exposure and production of proinflammatory cytokines. NHPSC and A431 were incubated with 0-10 mM MTX or alpha-MEM (control) in the presence or absence of 40 mM EtOH. A formazan 3-(4,5-dimethylthiazole-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used as a marker for cell viability (control was 100%). Significance was calculated by ANOVA. Cytokine release into media was quantitated by ELISA. After 24 h of MTX exposure, the release of IL-1alpha was unchanged. IL-6 increased 1.7 times in both cultures, and IL-8 increased 1.7 times in NHPSC and 2.1 times in A431. TNF-alpha release increased twice in A431 but not in NHPSC. Human recombinant IL-1alpha and IL-6 for 24 h had no effect, while TNF-alpha reduced cytoviability by 30% in NHPSC and 22% in A431. Anti-TNF-alpha reversed the effect produced by TNF-alpha in NHPSC and reduced it in A431 (11.8%, p < 0.05). We concluded that in vitro in normal human primary keratinocytes, toxicity and inflammatory responses are enhanced by EtOH.
 ...
PMID:Ethanol-modulated cytokine production and expression in skin cells exposed to methotrexate. 1032 85

Interleukin-8 (IL-8), a cytokine produced by a host of cells including monocytes, macrophages, Kupffer cells and hepatocytes, can activate neutrophils. Peripheral neutrophilia and liver neutrophil infiltration are frequently noted in patients with alcoholic liver disease (ALD). Serum IL-8 levels are markedly elevated in patients with alcoholic hepatitis compared with those in patients with alcoholic cirrhosis, alcoholic fatty liver and non-alcoholic liver disease. The levels are also elevated in patients who die of hepatic failure and correlate with biochemical and histologic parameters and severity of liver injury. Patients with high serum IL-8 had a higher mortality rate than those with lower levels. In liver tissue from patients with ALD, local IL-8 levels also correlated with the degree of neutrophil infiltration. Serum IL-8 levels decreased gradually with abstinence from alcohol. Ethanol can increase plasma endotoxin, a potent inducer of tumor necrosis factor (TNF)-alpha and IL-1. Subsequently, TNF-alpha and IL-1, together with endotoxin, stimulate circulating and local IL-8 in ALD. Activated IL-8 then mediates neutrophil infiltration, a pivotal process in the pathogenesis of ALD. IL-8 levels might reflect the stage and severity of ALD and might serve as a predictor of survival in patients with alcoholic hepatitis. The development of agents with an anti-IL-8 effect is promising for the therapy of ALD.
 ...
PMID:Interleukin-8 and alcoholic liver disease. 1041 75

Ethanol impairs immune responses in humans and animal models, in vivo and in vitro. In particular, ethanol inhibits some key functions of human polymorphonuclear neutrophils (PMN). We investigated the impact of ethanol on cytokine production by highly purified PMN. In a time- and concentration-dependent manner, ethanol inhibited the production of interleukin (IL)-8 protein and mRNA and also hindered tumor necrosis factor alpha (TNF-alpha) release by modulating the expression of the TNF-alpha-converting enzyme involved in TNF-alpha shedding. This disruption of PMN cytokine release by ethanol may contribute to the increased risk of infection in alcoholic patients. Degranulation of hepatocyte growth factor (HGF) was also impaired by a clinically relevant ethanol concentration (0.8%), an action that may delay the repair of alcoholic liver damage. These findings suggest that ethanol may modulate three major cytokines involved in alcoholic liver diseases, IL-8, TNF-alpha, and HGF, via three different mechanisms.
 ...
PMID:Ethanol-induced inhibition of cytokine release and protein degranulation in human neutrophils. 1248 95

Ethanol toxicity on liver is a function of duration of alcoholism, amount of daily intake of alcohol and patient's nutrition. The threshold of alcohol toxicity on the liver is about 40 g of ethanol daily in men and 20-30 g in women, however liver cirrhosis develops in no more than 8-20% of patients exceeding this values. Ethanol is oxidized in the liver to acetaldehyde--a compound considerably more toxic than ethanol itself. Despite small amount of alcohol dehydrogenase (ADH) found in gastric mucosa, the metabolism of ethanol in this site may have an important hepatoprotective effect. The oxidation of ethanol is associated with a change of hepatocyte redox homeostasis, which leads to a number of metabolic disorders such as lactic acidosis, hyperlipidaemia and hyperuricaemia. Chronic ethanol consumption does not influence ADH activity, but has a profound stimulatory effect on microsomal enzymes, in particular cytochrome CYP2E1. This fact is responsible for development in alcoholic liver associated with rise of oxygen consumption, excessive production of free radicals and increased metabolism of ethanol, vitamin A and testosterone. Ethanol and acetaldehyde have a deleterious effect, both the direct and indirect, on hepatocytes e.g., generating radical oxygen species and damaging intestinal mucosal barrier. Cellular oxidative stress that is caused by both an excess of free radicals and the antioxidatives' deficiency (glutathion, vitamin E, phosphatidylcholine), may be the principal factor responsible for progression of alcoholic liver disease. Among other factors accelerating alcohol-related liver lesion there are certain drugs, high fat diet, infection with HCV and genetic factors (female sex, enzymatic polymorphic forms of ADH and ALDH, hemochromatosis). Great importance in pathogenesis of necrotic and inflammatory hepatic events is being attributed to portal endotoxaemia and cytokines induced within the liver, in particular TNF-alpha and interleukin 8. These cytokines play a key role in development of alcoholic hepatitis, which clinical severity ranges from subclinical to fatal forms. Apart from abstinence, the treatment of alcohol liver disease is based on hyperalimentation, since alcoholism is generally associated with protein malnutrition. In severe forms of alcohol hepatitis corticosteroids are recommended.
 ...
PMID:[Alcoholic liver disease]. 1290 Dec 71

Immune system impairment and increased susceptibility to infection among alcohol abusers is a significant but not well-understood problem. We hypothesized that acute ethanol administration would inhibit leukocyte recruitment and endothelial cell activation during inflammation and infection. Using LPS and carrageenan air pouch models in mice, we found that physiological concentrations of ethanol (1-5 g/kg) significantly blocked leukocyte recruitment (50-90%). Because endothelial cell activation and immune cell-endothelial cell interactions are critical regulators of leukocyte recruitment, we analyzed the effect of acute ethanol exposure on endothelial cell activation in vivo using the localized Shwartzman reaction model. In this model, ethanol markedly suppressed leukocyte accumulation and endothelial cell adhesion molecule expression in a dose-dependent manner. Finally, we examined the direct effects of ethanol on endothelial cell activation and leukocyte-endothelial cell interactions in vitro. Ethanol, at concentrations within the range found in human blood after acute exposure and below the levels that induce cytotoxicity (0.1-0.5%), did not induce endothelial cell activation, but significantly inhibited TNF-mediated endothelial cell activation, as measured by adhesion molecule (E-selectin, ICAM-1, VCAM-1) expression and chemokine (IL-8, MCP-1, RANTES) production and leukocyte adhesion in vitro. Studies exploring the potential mechanism by which ethanol suppresses endothelial cell activation revealed that ethanol blocked NF-kappaB nuclear entry in an IkappaBalpha-dependent manner. These findings support the hypothesis that acute ethanol overexposure may increase the risk of infection and inhibit the host inflammatory response, in part, by blocking endothelial cell activation and subsequent immune cell-endothelial cell interactions required for efficient immune cell recruitment.
 ...
PMID:Ethanol blocks leukocyte recruitment and endothelial cell activation in vivo and in vitro. 1552 77

Alcohol abuse is associated with enhanced risk for pulmonary infections, but the mechanisms remain obscure. We assessed whether ethanol reduced generation of cytokines from a human lung epithelial cell line (A549) in vitro and if effects on the NFkappaB transcription factor were involved. Exposure of A549 to ethanol (0.1-1%) dose-dependently inhibited (by 15-49%) the release of G-CSF and IL-8, but not of M-CSF, triggered by IL1beta or TNFalpha. Ethanol also inhibited by 49% the IL-1beta stimulated translocation of the p65 subunit of NFkappaB from the cytoplasm into the nucleus. Using a kappaB binding and luciferase coupled construct, transfected into A549 cells, we found that 1% ethanol specifically reduced IL-1beta and TNFalpha induced luciferase activity with 34 and 40%, respectively. Thus, in vitro exposure of lung epithelial cells to ethanol reduced the generation of cytokines, as well as translocation and gene activation by NFkappaB.
 ...
PMID:Effects of ethanol on cytokine generation and NFkappaB activity in human lung epithelial cell. 1599 49

A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-beta)), and IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-alpha (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-beta (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-alpha, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-alpha was significantly related to albumin and prothrombin activity, whereas TGF-beta was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-beta.
 ...
PMID:Cytokines and lipid peroxidation in alcoholics with chronic hepatitis C virus infection. 1821 80

Moderate alcohol consumption is suggested to be associated with reduced inflammation and morbidity. Human adipose tissue (AT) and obesity is characterised by low-grade inflammation, so the present study wanted to investigate the effects of ethanol on inflammation in human AT in vitro. Subcutaneous human AT was incubated with ethanol [11-88 mM] under non- or LPS-stimulated [50mg/mL] conditions. Protein and mRNA levels of adiponectin, IL-6, IL-8, TNF-alpha, MCP-1, and CD68 were assessed using ELISA and real-time RT-PCR, respectively. Non-stimulated, ethanol incubations up to 24h increased adiponectin release and mRNA expression (p<0.01) and decreased IL-6 release in both short-term [1.5h] (p<0.05) and long-term [24h] (p<0.01) incubations. Ethanol decreased LPS-stimulated IL-6, IL-8, TNF-alpha, and MCP-1 dose-dependently (all p<0.01). Ethanol decreased CD68 mRNA (p<0.001), which correlated with the investigated adipokines (p<0.05) but not adiponectin (p>0.05). In conclusion, ethanol exerts anti-inflammatory effects in human AT, suggesting that ethanol may attenuate whole-body inflammation.
 ...
PMID:Ethanol exerts anti-inflammatory effects in human adipose tissue in vitro. 1884 Apr 98


1 2 Next >>