Enhanced CCL26 production by IL-4 through IFN-gamma-induced upregulation of type 1 IL-4 receptor in keratinocytes.
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-gamma, a Th1 cytokine, on eosinophilic skin inflammation is unclear. This study investigated the effects of IFN-gamma 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-gamma simultaneously, IL-4-induced CCL26 production was attenuated. In contrast, prior stimulation with IFN-gamma 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-gamma. This upregulation resulted in an enhanced IL-4-mediated cellular signal. These results indicate that IFN-gamma 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-gamma might modulate eosinophilic skin inflammation.
Nishi
Natsuko
N
Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Yamamoto
Shuichi
S
Ou
Weilin
W
Muro
Eriko
E
Inada
Yukiko
Y
Hamasaki
Yuhei
Y
D002460:Cell Line; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis*; D015854:Up-Regulation
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; C508598:IL4 protein, human; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007371:Interferon-gamma