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- W2109647771 abstract "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-kappaB activation or ICAM-1 and IL-8 mRNA levels. TNF stimulation induced p38 MAPK-dependent phosphorylation of MK2 and HSP27. MK2 silencing reduced ICAM-1 and IL-8 expression without influencing NF-kappaB 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 post-transcriptional 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." @default.
- W2109647771 created "2016-06-24" @default.
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- W2109647771 date "2008-09-01" @default.
- W2109647771 modified "2023-10-16" @default.
- W2109647771 title "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" @default.
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- W2109647771 doi "https://doi.org/10.1016/j.bbamcr.2008.04.009" @default.
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