Differential regulation of prostaglandin E biosynthesis by interferon-γ in colonic epithelial cells
Differential regulation of prostaglandin E biosynthesis by interferon-γ in colonic epithelial cells
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DOI：
10.1038/sj.bjp.0705719
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发表时间：
2004-04-01
影响因子：
7.3
通讯作者：
Ward, SG
中科院分区：
文献类型：
--
作者：
Wright, KL;Weaver, SA;Ward, SG
1 在结肠上皮细胞系 HT29 和气道上皮细胞系 A549 中评估了环加氧酶 (COX)-2 的表达和对促炎细胞因子 TNFα 和 IFNγ 的活性。2 TNFα 诱导 COX-2 mRNA、蛋白质和前列腺素 (PG)E-2 合成的浓度和时间依赖性上调。3 TNFα 与 IFNγ 的共同刺激导致 COX-2 减少mRNA 和蛋白质表达。4 IFNγ 对 TNFα 诱导的 COX-2 mRNA 的稳定性没有影响。5 同时添加 IFNg 可以显着增强 TNFα 诱导的 PGE(2) 生物合成，并且是 COX-2 依赖性的。6 IFNγ 和 TNFα 的组合诱导微粒体前列腺素 E 合酶 (mPGES)，与增强的 PGE(2) 合成相称。7 这些结果表明，就PGE(2)生物合成中，IFNγ在COX-2表达水平上起负调节作用，在mPGES表达水平上起正调节作用。这可能对 IFNγ 在炎症性疾病中的临床应用具有重要意义。
1 Cyclooxygenase (COX)-2 expression and activity in response to pro-inflammatory cytokines TNFalpha and IFNgamma was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549.2 TNFalpha induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E-2 synthesis.3 Co-stimulation of TNFalpha with IFNgamma resulted in reduced COX-2 mRNA and protein expression.4 IFNgamma had no effect on the stability of TNFalpha-induced COX-2 mRNA.5 TNFalpha-induced PGE(2) biosynthesis was significantly enhanced by the simultaneous addition of IFNg and was COX-2 dependent.6 The combination of IFNgamma and TNFalpha induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE(2) synthesis.7 These results suggest that, in terms of PGE(2) biosynthesis, IFNgamma plays a negative regulatory role at the level of COX-2 expression and a positive regulatory role at the level of mPGES expression. This may have important implications for the clinical use of IFNgamma in inflammatory diseases.