1.放射線照射による消化管粘膜傷害モデルを用いた上皮細胞再生機構の解析

概要

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Background: Signaling by IL-4 and IL-13 is transduced via a receptor complex of IL-13Rα1 and IL-4Rα chains. However, contribution of a putative decoy receptor of IL-13, IL-13Rα2, is not clear. The aim of this study was to determine the significance of Th2-type cytokines in the gastrointestinal (GI) epithelial cell repair system. Methods: We compared the tissue recovery in wild type (WT) and IL-4 receptor α deficient (IL-4R KO) mice following mucosal damage induced by 3 Gy-whole body γ-irradiation. The expression of IL-4, IL-13 and related molecules in the regenerative process were assessed. Results: Expression of IL-13Rα2 dramatically increased in myofibroblasts and fibroblasts on day 3. In contrast, in IL-4R KO mice, intestinal tissue repair after irradiation was delayed, and the transient upregulation of IL-13Rα2 was not seen. Injection of a soluble IL-13Rα2-immunoglobulin chimeric protein to both of WT and IL-4R KO mice resulted in the improvement of tissue recovery. Addition of IL-13 into primary tissue culture of the jejunum induced epithelial cell damage with decreased expression of membrane bound β-catenin. Conclusions: Our study demonstrated that IL-13 has a potential to induce epithelial cell damage, and IL-13Rα2 functions as a regulatory factor in the regeneration of intestinal epithelial cells.