TNF-alpha and IL-4 regulate expression of IL-13 receptor alpha2 on human fibroblasts |
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Authors: | Yoshikawa Mamoru Nakajima Toshiharu Tsukidate Toshiharu Matsumoto Kenji Iida Makoto Otori Nobuyoshi Haruna Shin-ichi Moriyama Hiroshi Saito Hirohisa |
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Institution: | Department of Allergy and Immunology, National Research Institute for Child Health and Development, 3-35-31 Taishidou, Setagaya-ku, 154-8567, Tokyo, Japan. |
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Abstract: | Two interleukin 13 receptors (IL-13Rs) have been identified as IL-13Ralpha1 and IL-13Ralpha2. IL-13Ralpha1 is composed of a heterodimer consisting of IL-13Ralpha1 and IL-4 receptor alpha (IL-4Ralpha) as a signaling subunit. In contrast, IL-13Ralpha2 is known as a decoy receptor for IL-13. In this study, we investigated the expression of IL-13Rs on human fibroblasts. IL-13Ralpha2 was significantly up-regulated after stimulation with tumor necrosis factor-alpha (TNF-alpha) and/or IL-4. In contrast, IL-13Ralpha1 was constitutively detectable and was not up-regulated. After the induction of IL-13alpha2 by IL-4, STAT6 phosphorylation through IL-13Ralpha1 by IL-13 was inhibited. We also detected large intracellular pools of IL-13Ralpha2 in fibroblasts quantitatively. Furthermore, mobilization of the IL-13Ralpha2 protein stores from the cytoplasm to the cell surface was prevented by an inhibitor of protein transport, brefeldin-A. These results indicate that TNF-alpha and IL-4 synergistically up-regulate the expression of IL-13Ralpha2 decoy receptor on human fibroblasts by inducing gene expression and mobilizing intracellular receptors, and thus may down-regulate the IL-13 signaling. |
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Keywords: | IL-13Rα2 Decoy receptor Human fibroblast TNF-α IL-4 Mobilization |
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