Enhanced CCL26 production by IL-4 through IFN-gamma-induced upregulation of type 1 IL-4 receptor in keratinocytes |
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Authors: | Nishi Natsuko Yamamoto Shuichi Ou Weilin Muro Eriko Inada Yukiko Hamasaki Yuhei |
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Affiliation: | Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan |
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Abstract: | A Th2 cytokine, IL-4, induces various chemokines from epidermal keratinocytes which play crucial roles in the pathogenesis of skin disorders such as atopic dermatitis. In contrast, the role of IFN-γ, a Th1 cytokine, on eosinophilic skin inflammation is unclear. This study investigated the effects of IFN-γ on IL-4-induced production of eotaxin-3/CCL26, a potent chemoattractant to eosinophils, in normal human epidermal keratinocytes (NHEK). When the cells were stimulated with IL-4 and IFN-γ simultaneously, IL-4-induced CCL26 production was attenuated. In contrast, prior stimulation with IFN-γ enhanced IL-4-induced CCL26 production. NHEK constitutively expressed type 1 IL-4 receptor, and expression at the cell surface was upregulated by stimulation with IFN-γ. This upregulation resulted in an enhanced IL-4-mediated cellular signal. These results indicate that IFN-γ has opposite effects on IL-4-induced CCL26 production in NHEK depending on the time of exposure. Thus, changes in IL-4R expression by IFN-γ might modulate eosinophilic skin inflammation. |
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Keywords: | Keratinocytes IL-4 IFN-γ IL-4R CCL26 |
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