Abstract
We have previously shown that expression of a Ca
2+
‐activated Cl
−
channel (mCLCA3 in mice and hCLCA1 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 hCLCA1 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 Ca
2+
‐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 in chronic pulmonary disorders.