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Biochem Biophys Res Commun. 2014 Mar 28;446(1):49-53. doi: 10.1016/j.bbrc.2014.02.051. Epub 2014 Feb 26.

Interleukin-13-induced MUC5AC expression is regulated by a PI3K-NFAT3 pathway in mouse tracheal epithelial cells.

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  • 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 2Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; State Key Lab. of Respiratory Disease (SKLRS), China. Electronic address: huahaoshen@163.com.

Abstract

Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction, while the mechanisms underlying this process are not fully elucidated. Previous studies showed that nuclear factor of activated T cells (NFAT) is involved in the pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus (particularly MUC5AC) production is still not clear. Here we showed that IL-13 specifically induced NFAT3 activation through promoting its dephosphorylation in air-liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs). Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC production, which both are known to be important in IL-13-stimulated mucus expression. Our study is the first to demonstrate that the PI3K-NFAT3 pathway is positively involved in IL-13-induced mucus production, and provided novel insights into the molecular mechanism of asthma mucus hypersecretion.

Copyright © 2014. Published by Elsevier Inc.

KEYWORDS:

Interleukin-13; MUC5AC; Nuclear factor of activated T cells 3; Phosphoinositide 3-kinase

[PubMed - indexed for MEDLINE]
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