TNF-alpha and IL-4 regulate expression of IL-13 receptor alpha2 on human fibroblasts.
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.
Yoshikawa
Mamoru
M
Department of Allergy and Immunology, National Research Institute for Child Health and Development, 3-35-31 Taishidou, Setagaya-ku, 154-8567, Tokyo, Japan.
Nakajima
Toshiharu
T
Tsukidate
Toshiharu
T
Matsumoto
Kenji
K
Iida
Makoto
M
Otori
Nobuyoshi
N
Haruna
Shin-ichi
S
Moriyama
Hiroshi
H
Saito
Hirohisa
H
D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000145:classification / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism*; D009928:Organ Specificity; D018123:Receptors, Interleukin / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C508181:IL13RA1 protein, human; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4