Endogenous metalloprotease solubilizes IL-13 receptor α2 in airway epithelial cells

IL-13 receptor alpha 2 (IL-13R alpha 2) has been postulated to be a decoy receptor. The precise mechanisms for the generation of soluble IL-13R alpha 2 and the biological activity of the endogenous soluble form have not been reported. Hypothesizing that the soluble form of IL-13R alpha 2 is generated by proteolytic cleavage of membrane-bound receptors, we transfected human airway epithelial cells with adenoviral vectors encoding full-length IL-13R alpha 2. Eotaxin production from IL-13R alpha 2-transfected cells was suppressed, and soluble IL-13R alpha 2 in the supernatants was increased time-dependently after the transfection. The transfer of conditioned media from IL-13R alpha 2-transfected cells inhibited IL-13-induced eotaxin production and STAT6 phosphorylation in non-transfected cells. PMA enhanced the release of soluble IL-13R alpha 2, and metalloprotease inhibitors inhibited this release. These findings suggest that airway epithelial cells with upregulation of membrane-bound IL-13R alpha 2 secrete soluble IL-13R alpha 2 into its supernatant, causing the autocrine and paracrine downregulation of the IL-13/STAT6 signal. Metalloprotease(s) are responsible for the proteolytic cleavage of cell surface IL-13R alpha 2. (C) 2007 Elsevier Inc. All rights reserved.