Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 1 (IL-1) induces prostanoid biosynthesis in endothelial cells by promoting cyclooxygenase expression, but little is known about its activity on the biosynthesis of hydroxyeicosatetraenoic acids (HETEs). We studied the effect of human recombinant IL-1 beta on the conversion of arachidonic acid (AA) to 15-HETE, a powerful inhibitor of the biosynthesis of proinflammatory eicosanoids. Cultured human umbilical vein endothelial cells were incubated with or without IL-1 beta prior to the addition of labeled AA. The eicosanoids produced were analyzed by RP-HPLC. Untreated cells produced little amounts of 15-HETE (6 +/- 3 pmol/10(6) cells), but IL-1 beta treated cells increased 15-HETE formation in a dose-dependent manner (4-5-fold at 10 U/ml IL-1). The production of HETEs by IL-1 beta was dependent on protein synthesis. Aspirin inhibited prostanoids, HHT and 11-HETE dose dependently, whereas it was unable to totally inhibit 15-HETE in IL-1 beta-treated cells (50-60%). Nordihydroguaiaretic acid, a general lipoxygenase inhibitor, preferably inhibited 15-HETE formation but also reduced the synthesis of the other eicosanoids in a dose-dependent manner. Indomethacin and ETYA completely suppressed prostanoids, 11-HETE and 15-HETE formation in resting and IL-1 beta-activated cells. Using specific 15-lipoxygenase oligonucleotides and the reverse transcriptase polymerase chain reaction technique, we were unable to evidence detectable 15-lipoxygenase mRNA both in resting and IL-1-activated endothelial cells. Overall, these results provide evidence that in human endothelial cells IL-1 beta increases 15-HETE production. Data strongly suggest that this effect is mediated by cyclooxygenase rather than 15-lipoxygenase activity or expression.
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PMID:Interleukin-1 increases 15-hydroxyeicosatetraenoic acid formation in cultured human endothelial cells. 769 Nov 82

15-lipoxygenase (15-LO) has been implicated in the inflammation of chronic bronchitis (CB), but it is unclear which of its isoforms, 15-LOa or 15-LOb, is primarily involved. To detect 15-LO gene (mRNA) and protein expression, we have applied in situ hybridization (ISH) and immunohistochemistry (IHC), respectively, to bronchial biopsies obtained from 7 healthy nonsmokers (HNS), 5 healthy smokers (HS), and 8 smokers with CB, and additionally include the airways of lungs resected from 11 asymptomatic smokers (AS) and 11 smokers with CB. Compared with HNS, biopsies in CB demonstrated increased numbers of 15-LOa mRNA+ cells (median: HNS = 31.3/mm(2) versus CB = 84.9/mm(2), P < 0.01) and protein+ cells (HNS = 2.9/mm(2) versus CB = 32.1/mm(2), P < 0.01). The HS group also showed a significant increase in protein+ cells (HNS = 2.9/mm(2) versus HS = 14/mm(2), P < 0.05). In the resected airways, 15-LOa protein+ cells in the submucosal glands of the CB group were more numerous than in the AS group (AS = 33/mm(2) versus CB = 208/mm(2); P < 0.001). 15-LOa mRNA+ and protein+ cells consistently outnumbered 15-LOb by approximately 7- and 5-fold, respectively (P < 0.01). Quantitative reverse transcriptase polymerase chain reaction of complementary biopsies confirmed the increased levels of 15-LOa in CB compared with that in either HNS or HS (P < 0.05). There was no difference between the subject groups with respect to 15-LOb expression. The numbers of cells expressing mRNA for 15-LOa in CB showed a positive association with those expressing interleukin (IL)-4 mRNA (r = 0.80; P < 0.01). We conclude that the upregulation of 15-LO activity in the airways of HS and of smokers with CB primarily involves the 15-LOa isoform: the functional consequences of its association the upregulation of IL-4 in chronic bronchitis requires further study.
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PMID:Gene expression and immunolocalization of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis. 1244 26