Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 464-469 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 360 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 24 2007 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Endogenous metalloprotease solubilizes IL-13 receptor α2 in airway epithelial cells. / Matsumura, Mikiko; Inoue, Hiromasa; Matsumoto, Takafumi; Nakano, Takako; Fukuyama, Satoru; Matsumoto, Koichiro; Takayama, Koichi; Saito, Makoto; Kawakami, Koji; Nakanishi, Yoichi.
In: Biochemical and Biophysical Research Communications, Vol. 360, No. 2, 24.08.2007, p. 464-469.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endogenous metalloprotease solubilizes IL-13 receptor α2 in airway epithelial cells
AU - Matsumura, Mikiko
AU - Inoue, Hiromasa
AU - Matsumoto, Takafumi
AU - Nakano, Takako
AU - Fukuyama, Satoru
AU - Matsumoto, Koichiro
AU - Takayama, Koichi
AU - Saito, Makoto
AU - Kawakami, Koji
AU - Nakanishi, Yoichi
PY - 2007/8/24
Y1 - 2007/8/24
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=34447103212&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.06.076
DO - 10.1016/j.bbrc.2007.06.076
M3 - Article
VL - 360
SP - 464
EP - 469
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -