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)

It has been reported that cigarette smoking worsens alcohol-induced gastric lesions through neutrophil infiltration. We hypothesize that IL-8, a potent chemotactic factor for neutrophil is likely to be involved in this ulcerogenic process. To evaluate this phenomenon, the ability of cigarette smoke extract (CSE) to induce endothelial cell expression of IL-8 was examined. Two different fractions (ethanol or chloroform soluble extracts) of CSE with their chemical types identified showed a time- and dose-dependent increase on IL-8 secretion from ECV304 cell line. Protein kinase C (PKC) inhibitor GF109203X had no effect on IL-8 response in basal secretion and also to these stimuli. Protein tyrosine kinase (PTK) inhibitor genistein and protein kinase A (PKA) inhibitor H8 at respective concentrations significantly reduced chloroform and ethanol soluble extract-induced IL-8 expression by about 34 and 35% respectively at 8 h after incubation. It is concluded that CSE increases IL-8 release from human endothelial cells through PTK and PKA activation.
 ...
PMID:Increased interleukin-8 expression by cigarette smoke extract in endothelial cells. 1113 64

Chronic alcoholism complicated by alcoholic liver disease is characterized by activation of the inflammatory response system. To evaluate the role of cytokines in the progress of alcoholic cirrhosis, we assessed serum level of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and the antiinflammatory cytokines IL-2, IL-10, and transforming growth factor (TGF)-beta in patients with compensated and decompensated alcoholic liver cirrhosis. Compensated alcoholic cirrhosis was characterized by increased IL-6 (6.3+/-2.9 vs. HP 2.2+/-1.4 pg/ml in controls) and decreased IL-10 (HP 4.1+/-3.5 vs. 6.4+/-5.4 pg/ml in controls). TNF-alpha, IL-8, and TGF-beta1 levels were comparable to those found in controls. In sera of patients with decompensated alcoholic liver cirrhosis, besides increased IL-6 (11.2+/-7.7 pg/ml), increased concentrations of TNF-alpha (25.1+/-4.5 vs. 9.1+/-7.0 pg/ml in controls) and IL-8 (171.7+/-294.0 vs. 2.7+/-2.9 pg/ml in controls) were also detected. TGF-beta1 and IL-10 levels were similar to those found in controls. These results strongly indicate that a significant derangement of the balance between proinflammatory and antiinflammatory signals is characteristic of compensated and especially of decompensated alcoholic cirrhosis.
Alcohol 2001 Jan
PMID:Serum cytokine levels in alcohol-related liver cirrhosis. 1128 49

Water extracts of the mycelial culture and fruiting bodies of Agaricus blazei Murill were fractionated by ethanol precipitation using various ethanol concentrations. Original water extracts from mycelia (Fraction A-0) and fruiting bodies (Fraction B-0) induced TNF-alpha secretion by macrophages derived from rat bone marrow. Fractions B-4 and B-5 obtained from ethanol precipitation of fruiting bodies using 44% and 50% ethanol, respectively, and Fraction B-6 obtained from the supernatant at 50% ethanol markedly induced TNF-alpha secretion. Similar effects were observed in IL-8 secretion by macrophages. Regarding nitric oxide (NO), Fraction B-5 induced a significant increase in NO secretion and Fractions B-4 and B-6 induced slightly NO secretion. Northern blot analysis showed that the increases in cytokine- and NO secretion were due to an increase in cytokine mRNAs or NO synthase mRNA. Therefore, it is concluded that Agaricus blazei Murill components which activate macrophages result in the induction of cytokine- and NO secretion in vitro.
 ...
PMID:Secretion of TNF-alpha, IL-8 and nitric oxide by macrophages activated with Agaricus blazei Murill fractions in vitro. 1148 52

Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to improve liver function tests in alcoholic patients. In the present work we have investigated the effect of metadoxine on some parameters of cellular damage in hepatocytes and hepatic stellate cells in culture treated with ethanol and acetaldehyde. HepG2 and CFSC-2G cells were treated with 50 mM ethanol or 175 microM acetaldehyde as initial concentration in the presence or absence of 10 microg ml(-1) of metadoxine. Twenty-four hours later reduced and oxidized glutathione content, lipid peroxidation damage, collagen secretion and IL-6, IL-8 and TNF- alpha secretion were determined. Our results suggest that metadoxine prevents glutathione depletion and the increase in lipid peroxidation damage caused by ethanol and acetaldehyde in HepG2 cells. In hepatic stellate cells, metadoxine prevents the increase in collagen and attenuated TNF- alpha secretion caused by acetaldehyde. Thus, metadoxine could be useful in preventing the damage produced in early stages of alcoholic liver disease as it prevents the redox imbalance of the hepatocytes and prevents TNF- alpha induction, one of the earliest events in hepatic damage.
 ...
PMID:Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture. 1171 74

Leukocyte infiltration in the liver is one of the most important features of alcoholic liver disease. However, in alcoholic hepatitis, the role of polymorphonuclear neutrophils (PMNs) in liver injury still remains to be fully elucidated. Furthermore, the migration of PMNs and their presence in the liver during alcoholic hepatitis have not been fully investigated. Up-regulation of chemokine secretion and adhesion molecule expression on effector cells (i.e., PMNs) and target cells (i.e., hepatocytes) are important factors in neutrophilic infiltration of the liver. The CXC chemokines--that is, interleukin (IL)-8 (in human beings), cytokine-induced neutrophil chemoattractant (CINC) (in rats), and KC (in mice)--are proneutrophilic agents. They are up-regulated during chronic--that is, several years of--alcohol use in human beings and in up to 30 weeks in experimental models of ethanol intoxication in mice and rats. Up-regulation of these chemokines in the circulation and tissues is also associated with enhanced neutrophilic infiltration in the liver. In the rat, the up-regulation of CXC chemokine production is time dependent. For example, after 16 weeks of feeding, up-regulation of CXC chemokine is observed, whereas after 32 weeks, CC chemokines are enhanced. Concomitantly, selective migration of PMNs and mononuclear cells is observed. In another model, in which both CXC and CC chemokines were enhanced after chronic ethanol use for 12 weeks in mice, neutrophilic and mononuclear/lymphocytic infiltrations were also seen. This model correlates closely with alcoholic hepatitis in human beings, characterized by increased IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 (MIP-1) and profound increases in neutrophils and lymphocytes in the liver.
Alcohol 2002 May
PMID:Neutrophilic infiltration in alcoholic hepatitis. 1206 32

Activated monocytes and macrophages have been postulated to play an important role in the pathogenesis of alcoholic liver disease (ALD). Monocyte activation can be documented by measurement of neopterin, adhesion cell molecules, and certain proinflammatory cytokines and chemokines. We first became interested in the role of monocytes and monocyte-derived cytokines in ALD in relation to altered zinc metabolism that occurs regularly in ALD. Patients with ALD have hypozincemia, which responds poorly to oral zinc supplementation. We have shown that in ALD monocytes make a low-molecular-weight substance that, when injected into rabbits, causes prominent hypozincemia. Subsequently, multiple cytokines [especially tumor necrosis factor (TNF) and interleukin (IL)-8] have been shown to be overproduced by monocytes in ALD. We initially showed that monocytes in ALD spontaneously produce TNF and overproduce TNF in response to a lipopolysaccharide (LPS) stimulus, and this could be attenuated by antioxidants in vitro and in vivo. Alterations in the endotoxin-binding protein LPS-binding protein, in CD14, and in the endotoxin receptor Toll-like receptor 4 all may play roles in enhanced proinflammatory cytokine signaling in ALD. Moreover, several groups have documented increased TNF receptor density in monocytes in ALD. Inadequate negative regulation of TNF occurs at multiple levels in ALD. This includes decreased monocyte production of the important antiinflammatory cytokine IL-10 and blunted response to the antiinflammatory properties of adenosine. Finally, generation of reactive oxygen species (which occurs during alcohol metabolism) and products of lipid peroxidation induce production of cytokines, such as TNF and IL-8. In conclusion, there are multiple overlapping potential mechanisms for enhanced proinflammatory cytokine production by monocytes in ALD. We postulate that activation of monocytes and macrophages with subsequent proinflammatory cytokine production plays an important role in certain metabolic complications of ALD and is a component of the liver injury of ALD.
Alcohol 2002 May
PMID:Monocyte activation in alcoholic liver disease. 1206 38

Differentially expressed nucleolar TGF-beta1 target (DENTT) is a novel member of the TSPY/TSPY-L/SET/NAP-1 (TTSN) superfamily that we have previously identified in human lung cancer cells. Here, we have investigated the expression of this protein in the adult mouse. By Western analysis, DENTT is highly expressed in the pituitary gland and moderately in the adrenals, brain, testis, and ovary. Immunohistochemical staining analysis for DENTT showed differential cytoplasmic and nuclear staining patterns in several cell types. The pituitary gland showed the highest level of immunostaining for DENTT, with strong cytoplasmic immunoreactivity in the anterior lobe, moderate levels in the posterior lobe, and a few cells showing nuclear staining in the intermediate lobe. In contrast, the intermediate lobe of the pituitary showed intense cytoplasmic staining for TGF-beta1. Nuclear and cytoplasmic staining for DENTT was present in the islets of Langerhans in the pancreas. Cytoplasmic staining for DENTT was particularly intense in the cortex of the adrenal gland, whereas the medulla showed weak nuclear staining. In the nervous system, the choroid plexus showed the highest immunoreactivity, with cortical motoneurons and Purkinje cells having relatively high levels of staining for DENTT as well. DENTT immunoreactivity was found in Leydig interstitial cells, Sertoli cells, and primary spermatocytes in the testis. In the female reproductive system, DENTT immunoreactivity was present in oocytes, thecal cells, and corpora lutea. The bronchial epithelium of the lung showed moderate levels of staining for DENTT localized to the cell nucleus. Additionally, three rodent pituitary cell lines (AtT20, GH3, and alphaT3-1, representing corticotropes, lactotropes, and gonadotropes, respectively) showed expression of DENTT. Addition of TGF-beta1 or serum to AtT20 cells increased DENTT protein production by 4 hr and, after reaching maximal levels at 2.4-fold above basal level by 8 hr, decreased, whereas no more than a 1.5-fold increase in DENTT protein occurred in GH3 or alphaT3-1 cells. Transient transfection studies showed that ectopic DENTT expression significantly increased the level of p3TP-Lux reporter transcription in AtT20 cells, but not in GH3 or alphaT3-1 cells. Interestingly, addition of TGF-beta1 had no significant effect on the ability of DENTT expression to influence p3TP-Lux reporter transcription in AtT20 cells. This report is the first detailed immunohistochemical examination of a member of the TTSN superfamily in the adult mouse. Expression of DENTT in endocrine tissues, nervous system, lung, oocytes, and thecal cells, in addition to the testis, suggests new roles for the TTSN superfamily. The differential patterns of expression of DENTT and TGF-beta1 in some tissues, including the pituitary, suggest that other factors are likely to be regulators of DENTT besides TGF-beta1.
 ...
PMID:Expression of differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) in adult mouse tissues. 1211 71

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

The aim of this work was to study the induction and secretion of interleukin 8 (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and secretion were determined in the presence of the toxics, and the effect of antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide dismutase and glutathione peroxidase activities were determined. Lipid peroxidation increased significantly only in Ac-treated cells. All toxics failed to decrease significantly the intracellular levels of reduced GSH. Catalase activity was diminished in all treatments, while other enzyme activities did not present changes. No change in peroxide production was found with any treatment. IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)-treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase chain reaction results correlated with secretion values. Our results show that Ac and LPS treatment produced an increased IL-8 induction and secretion. Oxidative stress and TNF-alpha are mediators in IL-8 response. This observation suggests that in the in vivo liver, the mechanism of ethanol-induced IL-8 production requires ethanol metabolism, and hepatocytes do not require the interaction among different populations of liver cells to respond.
 ...
PMID:Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide. 1280 41

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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>