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)

In order to gain insights into indomethacin-induced gastric injury, rats were fed with indomethacin (20 mg/kg), or alternatively, the primary cultures of rat gastric epithelial cells were cultured with different doses of indomethacin (1-1000 microM). Light microscopy, electron microscopy, fluorescence microscopy, TdT-mediated dUTP-biotin nick end labelling staining, ssDNA staining and DNA fragmentation assay were employed to evaluate the levels of gastric injury and apoptosis. Cells expressing inducible nitric oxide synthase (iNOS) and interleukin (IL)-8 were localized at the rat gastric mucosa by immunohistochemistry. Administration of indomethacin to rats caused apoptosis and injury of the gastric mucosal epithelial cells. Indomethacin also induced apoptosis of primary cultures of gastric epithelial cells in a dose-dependent manner. Cells expressing iNOS and IL-8 were detected at and around the sites of gastric injury in the indomethacin-fed rats, but not in the control rats. The induction of apoptosis by indomethacin in the primary cultures of gastric epithelial cells suggests that the direct apoptotic capacity of indomethacin. iNOS and IL-8 may be involved in this process.
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PMID:Apoptosis of rat gastric mucosa and of primary cultures of gastric epithelial cells by indomethacin: role of inducible nitric oxide synthase and interleukin-8. 1149 46

Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.
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PMID:Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB. 1168 50