Shp2 plays an important role in acute cigarette smoke-mediated lung inflammation

Fen-Fen Li, Jian Shen, Hui-Juan Shen, Xue Zhang, Rui Cao, Yun Zhang, Qiu Qui, Xi-Xi Lin, Yi-Cheng Xie, Lin-Hui Zhang, Yong-Liang Jia, Xin-Wei Dong, Jun-Xia Jiang, Meng-Jing Bao, Shanshan Zhang, Wen-Jiang Ma, Xi-Mei Wu, Huahao Shen, Qiang-Min Xie, Yuehai Ke
Journal of Immunology 2012 September 15, 189 (6): 3159-67
Cigarette smoke (CS), the major cause of chronic obstructive pulmonary disease, contains a variety of oxidative components that were implicated in the regulation of Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) activity. However, the contribution of Shp2 enzyme to chronic obstructive pulmonary disease pathogenesis remains unclear. We investigated the role of Shp2 enzyme in blockading CS-induced pulmonary inflammation. Shp2 levels were assessed in vivo and in vitro. Mice (C57BL/6) or pulmonary epithelial cells (NCI-H292) were exposed to CS or cigarette smoke extract (CSE) to induce acute injury and inflammation. Lungs of smoking mice showed increased levels of Shp2, compared with those of controls. Treatment of lung epithelial cells with CSE showed elevated levels of Shp2 associated with the increased release of IL-8. Selective inhibition or knockdown of Shp2 resulted in decreased IL-8 release in response to CSE treatment in pulmonary epithelial cells. In comparison with CS-exposed wild-type mice, selective inhibition or conditional knockout of Shp2 in lung epithelia reduced IL-8 release and pulmonary inflammation in CS-exposed mice. In vitro biochemical data correlate CSE-mediated IL-8 release with Shp2-regulated epidermal growth factor receptor/Grb-2-associated binders/MAPK signaling. Our data suggest an important role for Shp2 in the pathological alteration associated with CS-mediated inflammation. Shp2 may be a potential target for therapeutic intervention for inflammation in CS-induced pulmonary diseases.

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