Interleukin-9 and interleukin-13 augment UTP-induced Cl ion transport via hCLCA1 expression in a human bronchial epithelial cell line

Background IL-9 and IL-13 induce airway goblet cell metaplasia, which is associated with expression of a Ca2+-activated Cl channel, hCLCA1. Objective As UTP stimulates both mucin secretion and Cl ion transport via a Ca2+-dependent pathway, the purpose of this study is to determine whether IL-9 and IL-13 affect UTP-induced Cl ion transport in human bronchial epithelial cell line 16HBE cells, and if they do, to elucidate whether such an effect is associated with hCLCA1 expression. Methods The increases in short-circuit current (I-sc) in response to UTP were measured in the presence of amiloride by the Ussing chamber method. The morphology of epithelial cells was assessed by light microscopic findings, and hCLCA1 expression was investigated by immunocytochemistry and immunoblotting. Results UTP-induced increases in I-sc in the cells treated with IL-9 or IL-13 for 48 h were greater than those in non-treated cells, and the potency of IL-13 was greater than that of IL-9. Pre-treatment with Ca2+-activated Cl channel inhibitors diisothocyanatostilbene-2, 2-disulphonic acid and niflumic acid completely inhibited the augmenting effects of IL-9 and IL-13 on I-sc. The epithelial layer of the cells treated with IL-9 or IL-13 was thicker than that of non-treated cells. The expression of hCLCA1 protein was induced by IL-13 in a concentration-dependent manner. These effects of IL-13 were more potent than those of IL-9. Conclusion IL-9 and IL-13 augmented UTP-induced Cl ion transport, probably via proliferation of the cells with hCLCA1 expression, and IL-13 was more potent than IL-9 in producing such an effect in 16HBE cells.