The anti-malaria drug artesunate inhibits cigarette smoke and ovalbumin concurrent exposure-induced airway inflammation and might reverse glucocorticoid insensitivity
单位：[1]China Japan Friendship Hosp, Dept Resp Dis, Beijing 100029, Peoples R China[2]Chinese Acad Med Sci, Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China[3]China Japan Friendship Hosp, Inst Clin Med Sci, Beijing 100029, Peoples R China
Background: The anti-malaria drug artesunate has been shown to attenuate experimental allergic asthma via inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This study was to further determine the effects of artesunate on cigarette smoke and ovalbumin (OVA) concurrent exposure-induced airway inflammation, the related mechanism, and glucocorticoid insensitivity. Methods and results: In vivo: Female BALB/c mice concurrently exposed to cigarette smoke and OVA developed mixed eosinophilic and neutrophilic airway inflammation. Airway hyper-responsiveness, total and differential cell counts, and pro-inflammatory cytokine levels (interleukin (IL)-4, IL-8, IL-13 and tumor necrosis factor (TNF)-alpha.) in bronchoalveolar lavage fluid (BALF) were measured. Lung tissue sections were stained for histological analysis, and proteins were extracted for Western blotting. Artesunate reduced methacholine-induced airway hyper-responsiveness, suppressed pulmonary inflammation cell recruitment and IL-4, IL-8, IL-13 and TNF-alpha levels, selectively inhibited PI3K delta/Akt pathway, and restored HDAC2 activity. In vitro: BEAS-2B cells were exposed to cigarette smoke extract (CSE) for 6 h and then stimulated with TNF-alpha overnight. Glucocorticoid sensitivity was evaluated by the inhibition of TNF-alpha-induced 1L-8 production by dexamethasone. CSE reduced the effects of dexamethasone on TNF-alpha-induced IL-8 production in BEAS-2B cells, while artesunate reversed CSE-induced glucocorticoid insensitivity and restored HDAC2 deactivation induced by CSE. Conclusion: Artesunate ameliorated cigarette smoke and OVA concurrent exposure-induced airway inflammation, inhibited the PI3K delta/Akt pathway, restored HDAC2 activity, and reversed CSE-induced glucocorticoid insensitivity in BEAS-2B cells. These findings indicate that artesunate might play a protective role in asthma induced by cigarette smoke and glucocorticoid insensitivity. (C) 2015 Elsevier B.V. All rights reserved.
第一作者单位：[1]China Japan Friendship Hosp, Dept Resp Dis, Beijing 100029, Peoples R China[2]Chinese Acad Med Sci, Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China
通讯作者：
通讯机构：[1]China Japan Friendship Hosp, Dept Resp Dis, Beijing 100029, Peoples R China[2]Chinese Acad Med Sci, Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China
推荐引用方式(GB/T 7714)：
Luo Qiongzhen,Lin Jiangtao,Zhang Lu,et al.The anti-malaria drug artesunate inhibits cigarette smoke and ovalbumin concurrent exposure-induced airway inflammation and might reverse glucocorticoid insensitivity[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2015,29(2):235-245.doi:10.1016/j.intimp.2015.11.016.
APA：
Luo, Qiongzhen,Lin, Jiangtao,Zhang, Lu,Li, Hong&Pan, Lin.(2015).The anti-malaria drug artesunate inhibits cigarette smoke and ovalbumin concurrent exposure-induced airway inflammation and might reverse glucocorticoid insensitivity.INTERNATIONAL IMMUNOPHARMACOLOGY,29,(2)
MLA：
Luo, Qiongzhen,et al."The anti-malaria drug artesunate inhibits cigarette smoke and ovalbumin concurrent exposure-induced airway inflammation and might reverse glucocorticoid insensitivity".INTERNATIONAL IMMUNOPHARMACOLOGY 29..2(2015):235-245
