Post-transcriptional regulation of TNF-induced expression of ICAM-1 and IL-8 in human lung microvascular endothelial cells: An obligatory role for the p38 MAPK-MK2 pathway dissociated with HSP27
Post-transcriptional regulation of TNF-induced expression of ICAM-1 and IL-8 in human lung microvascular endothelial cells: An obligatory role for the p38 MAPK-MK2 pathway dissociated with HSP27
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DOI：
10.1016/j.bbamcr.2008.04.009
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发表时间：
2008-09-01
影响因子：
5.1
通讯作者：
Meng, Xianzhong
中科院分区：
文献类型：
--
作者：
Su, Xin;Ao, Lihua;Meng, Xianzhong
肿瘤坏死因子-α（TNF）诱导的人肺微血管内皮细胞（MVECs）炎症反应是急性肺损伤的早期事件。研究表明，p38丝裂原活化蛋白激酶（MAPK）、MAPK活化蛋白激酶2（MK2）和热休克蛋白27（HSP 27）参与其他细胞类型中促炎介质的表达。然而，它们在肺MVEC中TNF诱导的炎症反应中的作用尚未确定。本研究探讨了p38 MAPK、MK 2和HSP 27在TNF诱导的人肺MVECs表达ICAM-1和IL-8中的作用。抑制p38 MAPK可降低ICAM-1和IL-8的表达，但不影响NF-κ B激活ICAM-1和IL-8 mRNA水平。TNF刺激诱导MK 2和HSP 27的p38 MAPK依赖性磷酸化。MK 2沉默降低ICAM-1和IL-8表达，而不影响NF-κ B活化或ICAM-1和IL-8 mRNA水平。HSP 27沉默降低TNF刺激后细胞HSP 27水平和HSP 27磷酸化，但对ICAM-1和IL-8表达无影响。我们的研究首次证明，MK2介导的转录后调节p38 MAPK的TNF诱导的ICAM-1和IL-8在人肺MVECs的表达，这种调节由p38 MAPK/MK2途径是解离的HSP 27磷酸化。(c)2008 Elsevier B. V.保留所有权利。
The tumor necrosis factor-alpha (TNF)-induced inflammatory response in human lung microvascular endothelial cells (MVECs) is an early event in acute lung injury. Studies have shown that p38 mitogen-activated protein kinase (MAPK), MAPK-activated protein kinase 2 (MK2) and heat shock protein 27 (HSP27) are involved in the expression of pro- inflammatory mediators in other cell types. However, their role in the TNF-induced inflammatory response in lung MVECs has not been determined. We evaluated the role of p38 MAPK, MK2 and HSP27 in regulating the TNF-induced expression of ICAM-1 and IL-8 in human lung MVECs. Inhibition of p38 MAPK reduced ICAM-1 and IL-8 expression without influencing NF-kappa B activation OF ICAM-I and IL-8 mRNA levels. TNF stimulation induced p38 MAPK-dependent phosphorylation of MK2 and HSP27. MK2 silencing reduced ICAM-I and IL-8 expression without influencing NF-kappa B activation or ICAM-1 and IL-8 mRNA levels. HSP27 silencing reduced cellular HSP27 levels and HSP27 phosphorylation following TNF stimulation but had no effect on ICAM-1 and IL-8 expression. Our study demonstrates for the first time that MK2 mediates posttranscriptional regulation by p38 MAPK of the TNF-induced expression of ICAM-1 and IL-8 in human lung MVECs, and that this regulation by the p38 MAPK/MK2 pathway is dissociated from HSP27 phosphorylation. (c) 2008 Elsevier B.V. All rights reserved.