title: Endogenous metalloprotease solubilizes IL-13 receptor alpha2 in airway epithelial cells.
abstract: IL-13 receptor alpha2 (IL-13Ralpha2) has been postulated to be a decoy receptor. The precise mechanisms for the generation of soluble IL-13Ralpha2 and the biological activity of the endogenous soluble form have not been reported. Hypothesizing that the soluble form of IL-13Ralpha2 is generated by proteolytic cleavage of membrane-bound receptors, we transfected human airway epithelial cells with adenoviral vectors encoding full-length IL-13Ralpha2. Eotaxin production from IL-13Ralpha2-transfected cells was suppressed, and soluble IL-13Ralpha2 in the supernatants was increased time-dependently after the transfection. The transfer of conditioned media from IL-13Ralpha2-transfected cells inhibited IL-13-induced eotaxin production and STAT6 phosphorylation in non-transfected cells. PMA enhanced the release of soluble IL-13Ralpha2, and metalloprotease inhibitors inhibited this release. These findings suggest that airway epithelial cells with upregulation of membrane-bound IL-13Ralpha2 secrete soluble IL-13Ralpha2 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-13Ralpha2.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Matsumura
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Takafumi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takako
authors.initials: T
authors.lastname: Nakano
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Koichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000737:chemistry* / Q000378:metabolism*; D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
chemical_list: D053663:Interleukin-13 Receptor alpha2 Subunit; D045726:Metalloproteases; D013755:Tetradecanoylphorbol Acetate