Endogenous metalloprotease solubilizes IL-13 receptor α2 in airway epithelial cells
- 作者：Mikiko Matsumura ; Hiromasa Inoue ; Takafumi Matsumoto ; Takako Nakano ; Satoru Fukuyama ; Koichiro Matsumoto ; Koichi Takayama ; Makoto Saito ; Koji Kawakami ; Yoichi Nakanishi
- 关键词：Th2 cytokine ; Soluble receptor ; Protease ; Phorbol 12-myristate 13-acetate
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：24 August 2007
- 卷：360
- 期：2
- 页码：464-469
- 文件大小：276 K
摘要
IL-13 receptor α2 (IL-13Rα2) has been postulated to be a decoy receptor. The precise mechanisms for the generation of soluble IL-13Rα2 and the biological activity of the endogenous soluble form have not been reported. Hypothesizing that the soluble form of IL-13Rα2 is generated by proteolytic cleavage of membrane-bound receptors, we transfected human airway epithelial cells with adenoviral vectors encoding full-length IL-13Rα2. Eotaxin production from IL-13Rα2-transfected cells was suppressed, and soluble IL-13Rα2 in the supernatants was increased time-dependently after the transfection. The transfer of conditioned media from IL-13Rα2-transfected cells inhibited IL-13-induced eotaxin production and STAT6 phosphorylation in non-transfected cells. PMA enhanced the release of soluble IL-13Rα2, and metalloprotease inhibitors inhibited this release. These findings suggest that airway epithelial cells with upregulation of membrane-bound IL-13Rα2 secrete soluble IL-13Rα2 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-13Rα2.