The negative-feedback regulation of the IL-13 signal by the IL-13 receptor alpha2 chain in bronchial epithelial cells.
Bronchial asthma is a complex disease characterized by airway inflammation involving Th2 cytokines. Among Th2 cytokines, the significance of IL-13 in the pathogenesis of bronchial asthma has recently emerged. Particularly, the direct action of IL-13 on bronchial epithelial cells (BECs) is critical for generation of airway hyperresponsiveness. IL-13 has two binding units; the IL-13 receptor alpha1 chain transduces the IL-13 signal comprising a heterodimer with the IL-4R alpha chain, whereas the IL-13 receptor alpha2 chain (IL-13Ralpha2) is thought to act as a decoy receptor. However, it remains obscure how expression of these molecules is regulated in each cell. In this article, we analyzed the expression of these components in BECs. Either IL-4 or IL-13 induced intracellular expression of IL-13Ralpha2 in BECs, which was STAT6-dependent and required de novo protein synthesis. IL-13Ralpha2 expressed on the cell surface as a monomer inhibited the STAT6-dependent IL-13 signal. Furthermore, expression of IL-13Ralpha2 was induced in lung tissues of ovalbumin-induced asthma model mice. Taken together, our results suggested the possibility that IL-13Ralpha2 induced by its ligand is transferred to the cell surface by an unknown mechanism, and it down-regulates the IL-13 signal in BECs, which functions as a unique negative-feedback system for the cytokine signal.
Yasunaga
Shin'ichiro
S
Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1, Nabeshima, Saga 849-8501, Japan.
Yuyama
Noriko
N
Arima
Kazuhiko
K
Tanaka
Hiroyuki
H
Toda
Shuji
S
Maeda
Miyako
M
Matsui
Keiko
K
Goda
Chiho
C
Yang
Qing
Q
Sugita
Yuji
Y
Nagai
Hiroichi
H
Izuhara
Kenji
K
D000818:Animals; D001249:Asthma / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053660:Receptors, Interleukin-13
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4