Walker G, Kunz D, Pignat W, van den Bosch H, Pfeilschifter J
Department of Pharmacology, University of Basel, Switzerland.
FEBS Lett. 1995 May 8;364(2):218-22. doi: 10.1016/0014-5793(95)00402-u.
Renal mesangial cells express group II phospholipase A2 in response to two principal classes of activating signals that may interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) and agents that elevate cellular levels of cAMP such as forskolin, an activator of adenylate cyclase. Using pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor NF kappa B, we determined its role in cytokine--and cAMP--triggered group II PLA2 expression. Micromolar amounts of PDTC suppress the IL-1 beta- and TNF alpha-dependent, but not the forskolin-stimulated group II PLA2 activity in mesangial cells. Furthermore, PDTC inhibited the increase of group II PLA2 mRNA steady state levels in response to IL-1 beta and TNF alpha, while only marginally affecting forskolin-induced PLA2 mRNA levels. Our data suggest that NF kappa B activation is an essential component of the cytokine signalling pathway responsible for group II PLA2 gene regulation and that cAMP triggers a separate signalling cascade not involving NF kappa B. These observations may provide a basis to study the underlying mechanisms involved in the regulation of group II PLA2 gene expression.
肾系膜细胞会响应两类主要的激活信号而表达II型磷脂酶A2，这两类信号可能以协同方式相互作用。这两组激活剂包括炎性细胞因子，如白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNFα），以及能提高细胞内环磷酸腺苷（cAMP）水平的物质，如毛喉素（一种腺苷酸环化酶激活剂）。我们使用核因子NF-κB的强效抑制剂吡咯烷二硫代氨基甲酸盐（PDTC），来确定其在细胞因子和cAMP触发的II型磷脂酶A2表达中的作用。微摩尔量的PDTC可抑制系膜细胞中IL-1β和TNFα依赖性的II型磷脂酶A2活性，但不抑制毛喉素刺激的该酶活性。此外，PDTC抑制了因IL-1β和TNFα而导致的II型磷脂酶A2 mRNA稳态水平的升高，而对毛喉素诱导的磷脂酶A2 mRNA水平仅有轻微影响。我们的数据表明，NF-κB激活是细胞因子信号通路中负责II型磷脂酶A2基因调控的重要组成部分，而cAMP触发了一个不涉及NF-κB的独立信号级联反应。这些观察结果可能为研究II型磷脂酶A2基因表达调控的潜在机制提供基础。
