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Deletion of Shp2 in bronchial epithelial cells impairs IL-25 production in vitro, but has minor influence on asthmatic inflammation in vivo.


ABSTRACT: Shp2 played an important role in cigarette-smoke-mediated inflammation, surfactant homeostasis and asthmatic airway remodeling. However, whether shp2 plays a key role in epithelium-associated allergic reaction is still unknown. In this study, LPS and OVA were observed to induce the production of IL-25 in bronchial epithelial cells in vitro via the activation of MAPK p38 and JNK. Furthermore, blockage of Shp2 by its specific inhibitor PHPS1 or by siRNA-mediated depletion was found to reduce the production of IL-25 in epithelial cells as well as the up-regulated LPS-triggered activation of JNK but not p38. To confirm the role of intra-bronchial epithelial Shp2 in OVA-induced allergic reaction, we generated CC10-rtTA/(tetO)7-Cre/Shp2f/f mice, where Shp2 was conditionally knocked out in bronchial epithelial cells. Surprisingly, specific deletion of Shp2 in bronchial epithelial cells showed a mild but insignificant effect on the expressions of epithelium-derived cytokines as well as TH2 and TH17 polarization following allergen-induced murine airway inflammation. Collectively, our data suggested that deletion of Shp2 impaired IL-25 production in bronchial epithelial cells in vitro, but might yet have minor influence on OVA-induced allergic reaction in vivo.

SUBMITTER: Qiu Z 

PROVIDER: S-EPMC5421800 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Deletion of Shp2 in bronchial epithelial cells impairs IL-25 production in vitro, but has minor influence on asthmatic inflammation in vivo.

Qiu Zhangwei Z   Zhou Jiesen J   Liu Fang F   Qin Xuejun X   Dai Yuanrong Y   Ke Yuehai Y   Chen Zhihua Z   Li Wen W   Ying Songmin S   Shen Huahao H  

PloS one 20170508 5


Shp2 played an important role in cigarette-smoke-mediated inflammation, surfactant homeostasis and asthmatic airway remodeling. However, whether shp2 plays a key role in epithelium-associated allergic reaction is still unknown. In this study, LPS and OVA were observed to induce the production of IL-25 in bronchial epithelial cells in vitro via the activation of MAPK p38 and JNK. Furthermore, blockage of Shp2 by its specific inhibitor PHPS1 or by siRNA-mediated depletion was found to reduce the p  ...[more]

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