Endogenous metalloprotease solubilizes IL-13 receptor alpha2 in airway epithelial cells.
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.
Matsumura
Mikiko
M
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Inoue
Hiromasa
H
Matsumoto
Takafumi
T
Nakano
Takako
T
Fukuyama
Satoru
S
Matsumoto
Koichiro
K
Takayama
Koichi
K
Saito
Makoto
M
Kawakami
Koji
K
Nakanishi
Yoichi
Y
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
D053663:Interleukin-13 Receptor alpha2 Subunit; D045726:Metalloproteases; D013755:Tetradecanoylphorbol Acetate