INTERLEUKIN-1-BETA-MEDIATED AND TUMOR NECROSIS FACTOR-ALPHA-MEDIATED REGULATION OF ICAM-1 GENE-EXPRESSION IN ASTROCYTES REQUIRES PROTEIN-KINASE-C ACTIVITY
INTERLEUKIN-1-BETA-MEDIATED AND TUMOR NECROSIS FACTOR-ALPHA-MEDIATED REGULATION OF ICAM-1 GENE-EXPRESSION IN ASTROCYTES REQUIRES PROTEIN-KINASE-C ACTIVITY
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DOI：
10.1002/glia.440140404
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发表时间：
1995-08-01
期刊：
影响因子：
6.2
通讯作者：
BENVENISTE, EN
中科院分区：
文献类型：
--
作者：
BALLESTAS, ME;BENVENISTE, EN
星形胶质细胞是中枢神经系统 (CNS) 的主要神经胶质细胞，表达多种粘附分子，包括细胞间粘附分子 1 (ICAM-1)。这些分子对于白细胞运输至炎症部位以及淋巴细胞活化非常重要。 ICAM-1 由新生大鼠星形细胞组成型表达，促炎细胞因子白细胞介素 1 β (IL-1 β)、肿瘤坏死因子 α (TNF-α) 和干扰素 γ (IFN-γ) 增强表达，其中 IL-1 β 和 TNF-α 是最强的诱导剂。在这项研究中，我们检查了细胞因子 IL-1β 和 TNF-α 诱导的 ICAM-1 基因表达中涉及的第二信使的性质。我们的结果表明，与蛋白激酶 C (PKC) 相关的刺激物，例如佛波酯佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 和钙离子载体 A23187 会增加 ICAM-1 mRNA 表达，而环核苷酸类似物和 PKA 激动剂则没有效果。 PKC 的药理学抑制剂（例如 H7、H8 和 calphostin C）可抑制 IL-1 β 和 TNF-α 诱导的 ICAM-1 基因表达。用 PMA 长时间治疗星形胶质细胞会导致 PKC 亚型 α、δ 和 epsilon 出现时间依赖性下调，并伴随在 PMA 治疗后特定时间点由 IL-1 β、TNF-α 和 PMA 本身诱导的 ICAM-1 mRNA 表达减少。这些数据共同证明了各种 PKC 同工型在大鼠星形胶质细胞中 IL-1β 和 TNF-α 增强 ICAM-1 基因表达中的作用。 (C) 1995 Wiley-Liss, Inc.
Several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) are expressed by astrocytes, the predominant glial cell of the central nervous system (CNS). Such molecules are important in the trafficking of leukocytes to sites of inflammation, and in lymphocyte activation. ICAM-1 is constitutively expressed by neonatal rat astocytes, and expression is enhanced by the proinflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), with IL-1 beta and TNF-alpha being the strongest inducers. In this study, we have examined the nature of the second messengers involved in ICAM-1 gene expression induced by the cytokines IL-1 beta and TNF-alpha. Our results indicate that stimuli related to protein kinase C (PKC) such as the phorbol ester phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 increase ICAM-1 mRNA expression, whereas cyclic nucleotide analogs and PKA agonists have no effect. Pharmacologic inhibitors of PKC such as H7, H8, and calphostin C inhibit ICAM-1 gene expression inducible by IL-1 beta and TNF-alpha. Prolonged treatment of astrocytes with PMA results in a time-dependent downregulation of the PKC isoforms alpha, delta, and epsilon, and a concomitant diminution of ICAM-1 mRNA expression induced by IL-1 beta, TNF-alpha, and PMA itself at specific time points post-PMA treatment. These data, collectively, demonstrate a role for various PKC isoforms in IL-1 beta and TNF-alpha enhancement of ICAM-1 gene expression in rat astrocytes. (C) 1995 Wiley-Liss, Inc.