Pro-inflammatory cytokines stimulate mitogen-activated protein kinase subfamilies, increase phosphorylation of c-Jun and ATF2 and upregulate c-Jun protein in neonatal rat ventricular myocytes
Pro-inflammatory cytokines stimulate mitogen-activated protein kinase subfamilies, increase phosphorylation of c-Jun and ATF2 and upregulate c-Jun protein in neonatal rat ventricular myocytes
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DOI：
10.1006/jmcc.1999.1040
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发表时间：
1999-12-01
影响因子：
5
通讯作者：
Sugden, PH
中科院分区：
文献类型：
--
作者：
Clerk, A;Harrison, JG;Sugden, PH
促炎细胞因子在心脏的病理生理反应中可能很重要。我们研究了从新生大鼠心室分离的原代培养的肌细胞中，白介素 1 β (IL-1 β) 或肿瘤坏死因子 α (TNF α) 对三种丝裂原激活蛋白激酶 (MAPK) 亚家族 [c-Jun N 末端激酶 (JNK)、p38-MAPK 和细胞外反应激酶 (ERK)] 的激活作用。两种细胞因子均刺激 JNK 活性快速（10 分钟内最大）增加。尽管IL-1β对JNK的激活短暂地在1小时内恢复到对照值，但对TNFα的反应是持续的。 IL-1 β 和 TNF α。也刺激 p38-MAPK 磷酸化，但对 IL-1 β 的反应始终大于 TNF α。两种细胞因子均激活 ERK，但程度低于佛波醇摄入者诱导的程度。转录因子 c-Jun 和 ATF2 被 MAPK 磷酸化，并参与 c-Jun 的上调。 IL-1β和TNFα刺激c-Tun和ATF2的磷酸化。然而，IL-1β 诱导 c-Jun 蛋白的更大增加。蛋白激酶 C (PKC)（Ro318220、GF109203X）和 ERK 级联抑制剂 (PD98059) 可减弱 IL-1 beta 诱导的 c-Jun 增加，但 LY294002（磷脂酰肌醇 3' 激酶抑制剂）和 SB203580（p38-MAPK 抑制剂，也抑制某些 JNK）这些数据表明 IL-1 β 和 TNF α 的一些病理作用可能是通过 MAPK 级联介导的，并且 ERK 级联而不是 JNK 或 p38-MAPK 参与了 IL-1 β 的 c-Tun 上调 (C) 1999 学术出版社。
Pro-inflammatory cytokines may be important in the pathophysiological responses of the heart. We investigated the activation of the three mitogen-activated protein kinase (MAPK) subfamilies [c-Jun N-terminal kinases (JNKs), p38-MAPKs and extracellularly-responsive kinases (ERKs)] by interleukin-1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha) in primary cultures of myocytes isolated from neonatal rat ventricles. Both cytokines stimulated a rapid (maximal within 10 min) increase in JNK activity. Although activation of JNKs by IL-1 beta was transient returning to control values within 1 h, the response to TNF alpha was sustained. IL-1 beta and TNF alpha. also stimulated p38-MAPK phosphorylation, but the response to IL-1 beta was consistently greater than TNF alpha, Both cytokines activated ERKs, but to a lesser degree than that induced by phorbol eaters. The transcription factors, c-Jun and ATF2, are phosphorylated by the MAPKs and are implicated in the upregulation of c-Jun. IL-1 beta and TNF alpha stimulated the phosphorylation of c-Tun and ATF2. However, IL-1 beta induced a greater increase in c-Jun protein. Inhibitors of protein kinase C (PKC) (Ro318220, GF109203X) and the ERK cascade (PD98059) attenuated the increase in c-Jun induced by IL-1 beta, but LY294002 (an inhibitor of phosphatidylinositol 3' kinase) and SB203580 (an inhibitor of p38-MAPK, which also inhibits certain JNK ( isoforms) had no effect. These data illustrate that some of the pathological effects of IL-1 beta and TNF alpha may be mediated through the MAPK cascades. and that the ERK cascade, rather than JNKs or p38-MAPKs, are implicated in the upregulation of c-Tun by IL-1 beta. (C) 1999 Academic Press.