A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction

Yuhong Zhou, Michael Shapiro, Qu Dong, Jamila Louahed, Christine Weiss, ShanHong Wan, Qiming Chen, Carl Dragwa, Dawn Savio, Minxue Huang, Catherine Fuller, Yaniv Tomer, Nicholas C. Nicolaides, Michael McLane, Roy C Levitt

Research output: Chapter in Book/Report/Conference proceedingChapter

62 Scopus citations

Abstract

We have previously shown that expression of a Ca2+ -activated Cl- channel (mCLCA 3 in mice and hCLCA 1 in humans) is up-regulated along with goblet cell metaplasia and mucus overproduction in the lungs of interleukin 9 (IL9) transgenic mice, and in human primary lung cultures by IL4, IL13 and IL9. We show here that hCLCA 1 expression in NCI-H292 cells specifically induces soluble gel-forming mucin production. Moreover, niflumic acid (NFA), a blocker of hCLCA1-dependent Cl- efflux, inhibits MUC5A/C production in these cells. NFA treatment during natural antigen-exposure, where mCLCA3 is greatly up-regulated in the lung, significantly reduces airway inflammation, goblet cell metaplasia and mucus overproduction in vivo. These data suggest that this Ca2+ -activated Cl- channel plays an important role in epithelial-regulated inflammatory responses, including goblet cell metaplasia, and represents a potential novel therapeutic target for the control of mucus overproduction chronic pulmonary disorders.

Original languageEnglish
Title of host publicationNovartis Foundation Symposium
Pages150-170
Number of pages21
Volume248
StatePublished - Dec 1 2002
Externally publishedYes

Publication series

NameNovartis Foundation Symposium
Volume248

ASJC Scopus subject areas

  • Medicine(all)

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    Zhou, Y., Shapiro, M., Dong, Q., Louahed, J., Weiss, C., Wan, S., Chen, Q., Dragwa, C., Savio, D., Huang, M., Fuller, C., Tomer, Y., Nicolaides, N. C., McLane, M., & Levitt, R. C. (2002). A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction. In Novartis Foundation Symposium (Vol. 248, pp. 150-170). (Novartis Foundation Symposium; Vol. 248).