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
| Autor: | Ning Zou, Yong Song, David A. Fullerton, Guang-Yun Cai, Xin Su, Xiaoping Yang, Xianzhong Meng, Lihua Ao |
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| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
endocrine system MAP Kinase Signaling System ICAM-1 p38 mitogen-activated protein kinases HSP27 Heat-Shock Proteins HSP27 Protein Serine-Threonine Kinases Lung injury p38 Mitogen-Activated Protein Kinases Article MK2 Hsp27 Humans Protein kinase A Lung Molecular Biology Cells Cultured Heat-Shock Proteins Regulation of gene expression Human lung microvascular endothelial cells IL-8 biology Tumor Necrosis Factor-alpha Microcirculation Interleukin-8 Intracellular Signaling Peptides and Proteins Endothelial Cells Cell Biology Intercellular Adhesion Molecule-1 Neoplasm Proteins Cell biology Gene Expression Regulation siRNA biology.protein Tumor necrosis factor alpha Endothelium Vascular Mitogen-Activated Protein Kinases Molecular Chaperones |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783(9):1623-1631 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2008.04.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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