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

Bluetongue is an insect-transmitted viral disease of sheep and some species of wild ruminants. Infection of lung microvascular endothelial cells (ECs) is central to the pathogenesis of bluetongue virus (BTV) infection of ruminants, but it is uncertain as to why cattle are resistant to BTV-induced microvascular injury and bluetongue disease. Thus, in order to better understand the pathogenesis of BTV infection of cattle, mRNAs encoding a variety of inflammatory mediators were quantitated by real-time polymerase chain reaction in primary bovine lung microvascular ECs (BLmVECs) exposed to BTV and/or EC-derived mediators. BTV infection of BLmVECs significantly increased the transcription of genes encoding interleukin-1 (IL-1), IL-6, IL-8, cyclooxygenase-2, and inducible nitric oxide synthase. Treatment of BLmVECs with EC-lysates that contained BTV as well as cytokines increased both the incidence of apoptosis and expression of cellular adhesion molecules, as compared to infection of BLmVECs with BTV alone. Thus, BTV infection caused activation of BLmVECs with production of inflammatory mediators that alter the mechanism of cell death of BLmVECs and exert potentially potent effects on blood coagulation. The activities of BTV-induced-EC-derived inflammatory mediators likely contribute to the resistance of cattle to BTV-induced microvascular injury and bluetongue disease.
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PMID:Bluetongue virus-induced activation of primary bovine lung microvascular endothelial cells. 1200 81

Bluetongue is an insect-transmitted disease of sheep and wild ruminants that is caused by bluetongue virus (BTV). Cattle are asymptomatic reservoir hosts of BTV. Infection of lung microvascular endothelial cells (ECs) is central to the pathogenesis of BTV infection of both sheep and cattle, but it is uncertain as to why sheep are highly susceptible to BTV-induced microvascular injury, whereas cattle are not. Thus, to better characterize the pathogenesis of bluetongue, the transcription of genes encoding a variety of vasoactive and inflammatory mediators was quantitated in primary ovine lung microvascular ECs (OLmVECs) exposed to BTV and/or inflammatory mediators. BTV infection of OLmVECs increased the transcription of genes encoding interleukin- (IL) 1 and IL-8, but less so IL-6, cyclooxygenase-2, and inducible nitric oxide synthase. In contrast, we previously have shown that transcription of genes encoding all of these same mediators is markedly increased in BTV-infected bovine lung microvascular ECs and that BTV-infected bovine ECs produce substantially greater quantities of prostacyclin than do sheep ECs. Thus, sheep and cattle were experimentally infected with BTV to further investigate the role of EC-derived vasoactive mediators in the pathogenesis of bluetongue. The ratio of thromboxane to prostacyclin increased during BTV infection of both sheep and cattle, but was significantly greater in sheep (P = 0.001). Increases in the ratio of thromboxane to prostacyclin, indicative of enhanced coagulation, coincided with the occurrence of clinical manifestations of bluetongue in BTV-infected sheep. The data suggest that inherent species-specific differences in the production and activities of EC-derived mediators contribute to the sensitivity of sheep to BTV-induced microvascular injury.
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PMID:The role of endothelial cell-derived inflammatory and vasoactive mediators in the pathogenesis of bluetongue. 1206 31

Although nuclear factor (NF)-kappaB plays a central role in mediating cytokine-stimulated human inducible nitric-oxide synthase (hiNOS) gene transcription, very little is known about the factors involved in silencing of the hiNOS promoter. NF-kappaB-repressing factor (NRF) interacts with a specific negative regulatory element (NRE) to mediate transcriptional repression of certain NF-kappaB responsive genes. By sequence comparison with the IFN-beta and IL-8 promoters, we identified an NRE in the hiNOS promoter located at -6.7 kb upstream. In A549 and HeLa human cells, constitutive NRF mRNA expression is detected by RT-PCR. Gel shift assay showed constitutive NRF binding to the hiNOS NRE. Mutation of the -6.7-kb NRE site in the hiNOS promoter resulted in loss of NRF binding and increased basal but not cytokine-stimulated hiNOS transcription in promoter transfection experiments. Interestingly, overexpression of NRF suppressed both basal and cytokine-induced hiNOS promoter activity that depended on an intact cis-acting NRE motif. By using stably transformed HeLa cells with the tetracycline on/off expression system, reduction of cellular NRF by expressing antisense NRF increased basal iNOS promoter activity and resulted in constitutive iNOS mRNA expression. These data demonstrate that the transacting NRF protein is involved in constitutive silencing of the hiNOS gene by binding to a cis-acting NRE upstream in the hiNOS promoter.
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PMID:Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: The role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene. 1238 93

H. pylori colonisation of the stomach causes the recruitment of the inflammatory cells by the adherence of the bacteria with the epithelium and the release of factors of virulence either to the contact (oipA or other soluble factors) or in the cell by translocation (CagA). Such contact triggers interleukin 8 expression in the epithelial cell and attracts lymphocytes and monocytes into the chorion. Bacterial lipopolysaccharide and urease support the activation of these inflammatory cells. The lymphocytes produce pro-inflammatory cytokines, which direct the immune response towards the Th1 pathway. The variability of the inflammatory response depends on hereditary factors of the host such as the interleukin 1 genotypes, which determine the level of the pro-inflammatory cytokine expression, and of bacterial factors such as the cag pathogenicity island, the lipopolysaccharide and the vacuolating toxin, vacA. The mucosal inflammation provokes apoptosis and atrophy of the epithelial cells through the effect of pro-inflammatory cytokines and free radicals. Epithelial proliferation is a consequence of excessive apoptosis caused by the infection. It is stimulated by the expression of inducible cyclo-oxygenase and inducible nitric oxide synthase. The development of atrophic gastritis towards cancer is supported by nitric oxide which has a mutagenic effect on DNA and inhibits p53 protein and by the bacterium itself which decreases DNA mismatch repairing activity. The gastritis induced by Helicobacter pylori changes acid secretion according to the prevalent location of the gastritis in the antrum or in the gastric body. Prevalent gastritis in the gastric body causes hypochlorhydria by reducing the release of histamin from ECL cells and inhibiting the parietal cells through the effect of tumor necrosis factor and interleukin 1-beta. Hypochlorhydria is more marked among patients having a pro-inflammatory genotype for interleukin 1-beta and those infected by bacteria with virulence factors. In the event of antrum predominant gastritis, the pro-inflammatory cytokines cause a reduction of somatostatin and gastrin releases from the D and the G cells, respectively. The result of all is increased maximal acid output and the meal-stimulated acid secretion.
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PMID:[What are the gastric modifications induced by acute and chronic Helicobacter pylori infection?]. 1270 Apr 95

Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.
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PMID:Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation. 1291 42

The pro-inflammatory cytokine interleukin-1beta (IL-1) induces articular chondrocytes to produce reactive oxygen species (ROS), including hydrogen peroxide (H2O2), which mediate some IL-1-induced responses. This study aimed at elucidating the role of ROS, particularly H2O2, in mediating IL-1-induced activation of the transcription factor activator protein-1 (AP-1) in primary cultures of articular chondrocytes. AP-1 may function either as an inducer or as a repressor of the inducible nitric oxide synthase (iNOS) gene promoter. Since we observed that AP-1 is not required for iNOS expression in chondrocytes, we also investigated whether it is a repressor of this gene. The results of electrophoretic mobility shift assays showed that both IL-1 and H2O2 activated AP-1 and that inhibition of IL-1-induced ROS production abrogated AP-1 activation. The AP-1 complexes, induced by either IL-1 or H2O2, contained c-Fos/c-Jun and c-Fos/JunD heterodimers, but IL-1 activated AP-1 with a kinetics slower than that observed with H2O2. Pre-activation of AP-1, before stimulation of the cells with IL-1, did not inhibit iNOS mRNA and protein synthesis, relative to cells treated with IL-1 alone. These results indicate that H2O2 is a major mediator of IL-1-induced AP-1 activation in articular chondrocytes and that inhibition of ROS production is an effective strategy to block this IL-1-induced response. This study also identifies c-Fos/c-Jun and c-Fos/JunD heterodimers as the AP-1 transcription factors induced by IL-1, which, although not involved in the transcriptional regulation of the iNOS gene, may be important for the regulation of other genes also relevant in arthritic diseases, namely the collagenase-1 and IL-8 genes.
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PMID:Hydrogen peroxide mediates interleukin-1beta-induced AP-1 activation in articular chondrocytes: implications for the regulation of iNOS expression. 1468 13

By means of semi-quantitative RT-PCR, expression of a number of immune relevant genes was studied in skin of small rainbow trout Oncorhynchus mykiss (Walbaum, 1792) fry during both primary and secondary infections with the ectoparasitic monogenean Gyrodactylus derjavini Mikailov, 1975. The target genes studied included the cyto- and chemokines TNF-alpha1, TNF-alpha2, TGF-beta and IL-8, the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) genes and finally, two cell markers, the beta-chains of TCR and MHC II, from the adaptive arm of the immune system. In general, constitutive expression of all studied genes was apparent. Significant increases in expression of the TNF-alpha1 isoform could be observed at day 8 p.i. in primary infections and although less marked, the alpha2 isoform of TNF showed a similar trend. With the cytokine TGF-beta, 8-10 times increase in the transcription levels was observed in secondary infections compared to uninfected hosts. However, no parasite related changes in expression patterns could be observed for IL-8. Parasite infections elicited strong iNOS expression by 4 days p.i., but significant differences were not detected before day 8 p.i., when transcript levels were increased 5.5-9.6 times compared to uninfected controls. Augmented expression of COX-2 could also be observed in primary, but not secondary, infections at later stages of infections. No clear parasite related changes in transcript levels of the two cell markers TCRbeta and MHC IIbeta could be observed. Although the cellular source(s) was not determined, most of the examined factors appear to take part in a local signalling network of pivotal importance for the initiation, orchestration, effectuation and modulation of immune responses in rainbow trout against the ectoparasite G. derjavini.
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PMID:Expression of immune response genes in rainbow trout skin induced by Gyrodactylus derjavini infections. 1474 Nov 33

1. Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite. 2. Diosmectite (500 mg x kg(-1) day(-1), p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination. 3. Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1beta (IL-1beta) and leukotriene B(4) synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50 mg x kg(-1) day(-1)). 4. 5. Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells. Diosmectite had a dose-dependent inhibitory effect on IL-1beta production by LPS-stimulated THP-1 cells. 6. The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells. 7. Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.
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PMID:Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat. 1499 5

Inducible nitric oxide (NO) synthase (iNOS) appears to be a marker of tumor progression in colon carcinogenesis. Here we investigated effects of NO on selected chemokines that differentially regulate angiogenesis, namely pro-angiogenic interleukin (IL)-8 as well as tumor-suppressive interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG). These chemokines are expressed by DLD-1 colon carcinoma cells after stimulation with IL-1beta/interferon-gamma. Expression of IL-8 was markedly upregulated by NO. Moreover, NO enhanced expression of vascular endothelial growth factor (VEGF). In contrast, expression of IP-10 and MIG was suppressed by NO. The present data are consistent with previous observations that link NO to enhanced tumor angiogenesis and imply that NO-mediated upregulation of IL-8 and VEGF as well as downregulation of IP-10 and MIG may contribute to this phenomenon.
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PMID:Nitric oxide differentially regulates pro- and anti-angiogenic markers in DLD-1 colon carcinoma cells. 1506 30

Resveratrol (3,4',5-trihydroxystilbene) is a polyphenolic stilbene found in the skins of red fruits, including grapes, that may be responsible for some of the health benefits ascribed to consumption of red wine. Resveratrol has been shown to have antioxidant properties and can act as an estrogen agonist. This study examined the anti-inflammatory effects of resveratrol on human airway epithelial cells. Resveratrol and the related molecule quercetin, but not deoxyrhapontin, inhibited IL-8 and granulocyte-macrophage colony-stimulating factor release from A549 cells. Neither the estrogen receptor antagonist tamoxifen nor the glucocorticoid antagonist mifepristone altered the inhibitory effect of resveratrol. The mechanism of resveratrol action was investigated further using luciferase reporter genes stably transfected into A549 cells. Resveratrol and quercetin inhibited NF-kappaB-, activator protein-1-, and cAMP response element binding protein-dependent transcription to a greater extent than the glucocorticosteroid dexamethasone. These compounds also had no significant effect on acetylation or deacetylation of core histones. Resveratrol, but not estradiol or N-acetyl cysteine, inhibited cytokine-stimulated inducible nitric oxide synthase expression and nitrite production (IC50 = 3.6 +/- 2.9 microM) in human primary airway epithelial cells. Resveratrol also inhibited granulocyte-macrophage colony-stimulating factor release (IC50 = 0.44 +/- 0.17 microM), IL-8 release (IC50 = 4.7 +/- 3.3 microM), and cyclooxygenase-2 expression in these cells. This study demonstrates that resveratrol and quercetin have novel nonsteroidal anti-inflammatory activity that may have applications for the treatment of inflammatory diseases.
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PMID:Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. 1518 Sep 20


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