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Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice
Author(s) -
Hua Wen,
Liu Hui,
Xia LiXia,
Tian BaoPing,
Huang HuaQiong,
Chen ZhiYang,
Ju ZhenYu,
Li Wen,
Chen ZhiHua,
Shen HuaHao
Publication year - 2015
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12554
Subject(s) - eosinophil , immunology , pi3k/akt/mtor pathway , allergic inflammation , inflammation , medicine , ovalbumin , bone marrow , immune system , biology , microbiology and biotechnology , signal transduction , asthma
Background and objective The mammalian target of rapamycin ( mTOR ) signalling pathway regulates immune responses, and promotes cell growth and differentiation. Inhibition of mTOR with rapamycin modulates allergic asthma, while the underlying molecular mechanisms remain elusive. Here, we demonstrate that rapamycin, effectively inhibits eosinophil differentiation, contributing to its overall protective role in allergic airway inflammation. Methods Rapamycin was administered in a mouse model of ovalbumin‐induced allergic airway inflammation, and the eosinophil differentiation was analysed in vivo and in vitro . Results Rapamycin significantly attenuated allergic airway inflammation and markedly decreased the amount of eosinophils in local airways, peripheral blood and bone marrow, independently of levels of interleukin‐5 ( IL ‐5). In vitro colony forming unit assay and liquid culture demonstrated that rapamycin directly inhibited IL ‐5‐induced eosinophil differentiation. In addition, rapamycin reduced the production of IL ‐6 and IL ‐13 by eosinophils. Rapamycin was also capable of reducing the eosinophil levels in IL ‐5 transgenic NJ .1638 mice, again regardless of the constitutive high levels of IL ‐5. Interestingly, rapamycin inhibition of eosinophil differentiation in turn resulted in an accumulation of eosinophil lineage‐committed progenitors in bone marrow. Conclusions Altogether these results clearly demonstrate a direct inhibitory role of rapamycin in eosinophil differentiation and function, and reemphasize the importance of rapamycin and possibly, mTOR , in allergic airway disease.