Open AccessDeletion of Shp2 in bronchial epithelial cells impairs IL-25 production in vitro, but has minor influence on asthmatic inflammation in vivo
Author(s) -
Zhangwei Qiu,
Jia Zhou,
Fang Liu,
Xuejun Qin,
Yuanrong Dai,
Yuehai Ke,
Zhihua Chen,
Wen Li,
Songmin Ying,
Huahao Shen
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0177334
Subject(s) - inflammation , p38 mitogen activated protein kinases , in vivo , immunology , in vitro , epithelium , microbiology and biotechnology , respiratory epithelium , allergic inflammation , biology , chemistry , mapk/erk pathway , kinase , biochemistry , genetics
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/Shp2 f/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 .