人腹膜间皮细胞前列腺素合成：腹膜巨噬细胞衍生细胞因子对环氧化酶mRNA的诱导作用。

Human peritoneal mesothelial cell prostaglandin synthesis: induction of cyclooxygenase mRNA by peritoneal macrophage-derived cytokines.

作者信息

Topley N, Petersen M M, Mackenzie R, Neubauer A, Stylianou E, Kaever V, Davies M, Coles G A, Jörres A, Williams J D

机构信息

Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, United Kingdom.

出版信息

Kidney Int. 1994 Sep;46(3):900-9. doi: 10.1038/ki.1994.348.

DOI:10.1038/ki.1994.348

PMID:7996812

Abstract

Increasing evidence suggests that the mesothelial cell contributes to the control of inflammation in both the normal and inflamed peritoneal cavity. The present study examines the regulation of prostaglandin production by human peritoneal mesothelial cells (HPMC) following stimulation with peritoneal macrophage-conditioned medium and the cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). IL-1 beta and TNF-alpha stimulated significant release of prostaglandin above background levels in a time and dose dependent manner. Stimulation of HPMC with IL-1 beta (500 pg/ml) or TNF-alpha (100 pg/ml) for 24 hours resulted in the release of 24.5 +/- 4.3 (N = 11) (z = 3.40, P < 0.001 vs. control) and 19.4 +/- 4.5 (N = 10; z = 3.29, P < 0.001 vs. control) pg 6-keto-PGF1 a/micrograms cellular protein, respectively. Pretreatment of HPMC with dexamethasone (10(-6) to 10(-9) M) inhibited both constitutive and cytokine stimulated prostaglandin synthesis in a dose dependent manner. Both PMø-CM and PMø-S.epiCM stimulated 6-keto-PGF1 alpha and PGE2 synthesis by HPMC in a time and dose dependent manner (PMø-S.epiCM >> PMø-CM). Co-incubation of HPMC with PMø-S.epiCM in the presence of anti-IL-1 beta and/or anti-TNF-alpha antibody, interleukin-1 receptor antagonist or soluble TNF receptor (TNF p75) significantly reduced the capacity of these supernatants to stimulate prostaglandin synthesis. Exposure of HPMC to cytokines or PMø-S.epiCM resulted in the time dependent increase in the levels of both Cox-1 and Cox-2 mRNA as assessed by RT/PCR analysis with the greatest increase being seen for Cox-2. These data demonstrate specific stimulation of eicosanoid metabolism in HPMC by peritoneal macrophage derived cytokines, indicating the possible importance of these mediators in the activation of intraperitoneal prostaglandin synthesis. HPMC prostaglandins might act as important pro/anti-inflammatory mediators contributing to a cytokine network in the peritoneal cavity during CAPD peritonitis.

摘要

越来越多的证据表明，间皮细胞在正常和发炎的腹膜腔中都有助于控制炎症。本研究检测了人腹膜间皮细胞（HPMC）在受到腹膜巨噬细胞条件培养基以及细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）刺激后前列腺素产生的调节情况。IL-1β和TNF-α以时间和剂量依赖的方式刺激前列腺素释放至显著高于背景水平。用IL-1β（500 pg/ml）或TNF-α（100 pg/ml）刺激HPMC 24小时，分别导致释放24.5±4.3（N = 11）（z = 3.40，与对照组相比P < 0.001）和19.4±4.5（N = 10；z = 3.29，与对照组相比P < 0.001）pg 6-酮-PGF1α/微克细胞蛋白。用皮质醇（10⁻⁶至10⁻⁹ M）预处理HPMC以剂量依赖的方式抑制组成型和细胞因子刺激的前列腺素合成。腹膜巨噬细胞条件培养基（PMø-CM）和腹膜巨噬细胞上清条件培养基（PMø-S.epiCM）均以时间和剂量依赖的方式刺激HPMC合成6-酮-PGF₁α和PGE₂（PMø-S.epiCM >> PMø-CM）。在抗IL-1β和/或抗TNF-α抗体、白细胞介素-1受体拮抗剂或可溶性TNF受体（TNF p75）存在的情况下，将HPMC与PMø-S.epiCM共同孵育可显著降低这些上清液刺激前列腺素合成的能力。通过RT/PCR分析评估，HPMC暴露于细胞因子或PMø-S.epiCM导致Cox-1和Cox-² mRNA水平随时间依赖性增加，其中Cox-2的增加最为明显。这些数据表明腹膜巨噬细胞衍生的细胞因子对HPMC中类花生酸代谢有特异性刺激作用，表明这些介质在腹膜内前列腺素合成激活中可能具有重要性。HPMC前列腺素可能作为重要的促炎/抗炎介质，在持续性非卧床腹膜透析（CAPD）腹膜炎期间参与腹膜腔中的细胞因子网络。