Enhancement of P2Y6-Induced Cl- Secretion by IL-13 and Modulation of SK4 Channels Activity in Human Bronchial Cells

Abstract

Expression of functional P2Y₆ receptors was demonstrated in primary cultures of human bronchial cells (NHBE cells). P2Y₆ receptors were located only on the apical membranes of NHBE cells. Their stimulation by UDP induced a chloride secretion (short-circuit current) reflected by the development of two I_sc components (I_fast and I_late). A pharmacological characterization of those two I_sc components showed the involvement of CaCC and CFTR channel activity in I_fast and I_late respectively. I_fast was also found to be under control of basolateral SK4 channels. Indeed, inhibition of SK4 channels opening by clotrimazole dramatically reduced I_fast amplitude. The epithelial ion transporting phenotype depends on the cellular state of differentiation. As previously reported, we observed that Ultroser G increased the epithelial tightness and Na⁺-transport capacity while IL-13 switch the epithelial ion transport phenotype from a Na⁺-absorbing to a Cl^--secreting one. In our study, we report for the first time a change in the K⁺ cell permeability associated to IL-13-induced cell differentiation. IL-13 treatment increased the-resting K⁺ permeability as well as the Ca²⁺-dependent K⁺ permeability stimulated by UDP or ionomycin. SK4 channels activity, underlying the Ca²⁺-dependent K⁺ permeability was in particular increased by IL-13. The on/off effect of IL-13 on P2Y₆-induced Cl-secretion may help to identify the molecular determinants responsible for the CaCC channel activity.