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Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R

摘要:

Background Human antigen R (HuR) is a ubiquitously expressed member of the ELAV family,and has relatively high cytoplasmic abundance in lung tissue regenerating after injury.In this study,we investigated whether mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) and HuR participate in the tumor necrosis factor (TNF)-induced expression of interleukin-6 (IL-6).Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNA-mediated knockdown of MK2 or HuR.Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points.The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D.Finally,after knockdown of MK2,the cytoplasmic expression of HuR protein was analyzed using Western blotting.Results MK2 or HuR knockdown decreased both the mRNA and protein expression of Ik-6 in TNF-stimulated cells.In MK2 knockdown cells,the half-life of IL-6 mRNA was reduced to 36 minutes,compared with 67 minutes in the control group.In HuR knockdown cells,the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes.Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm.Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.

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作者单位: Department of Respiratory Medicine,Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing, Jiangsu 210028, China [1] Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China [2] Department of Respiratory Medicine, Lianyungang First People's Hospital, Lianyungang, Jiangsu 222002, China [3]
期刊: 《中华医学杂志(英文版)》2013年126卷22期 4322-4326页 SCIMEDLINEISTICCSCDBP
栏目名称: ORIGINAL ARTICLES
DOI: 10.3760/cma.j.issn.0366-6999.20130049
发布时间: 2014-01-08
基金项目:
This study was supported by the National Natural Science Foundation of China the Natural Science Foundation of Jiangsu Province the Medical Technology Innovation Foundation of Nanjing Military Command
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