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IL28RA inhibits human epidermal keratinocyte proliferation by inhibiting cell cycle progression.
Mol Biol Rep; 46(1): 1189-1197, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30632069
ABSTRACT
Interleukin (IL) 28 receptor α (IL28RA) is a well-known candidate for psoriasis susceptibility based on previous genome-wide association study (GWAS) analysis. However, the function of IL28RA in psoriasis has not been elucidated. In the present study, the expression of IL28RA was significantly decreased in lesional tissues from patients with plaque psoriasis when compared with the expression observed in adjacent non-lesional tissues. In vitro studies further demonstrated that in the presence of IL-29, HaCaT keratinocytes with IL28RA knockdown exhibited a faster rate of proliferation than control cells, and an enhanced ratio of cells in the S and G2/M phase. By contrast, IL28RA overexpression inhibited the proliferation of HaCaT keratinocytes and caused cell cycle arrest at the G0/G1 phases. Western blot analysis revealed that knockdown of IL28RA upregulated cyclinB1 expression and downregulated cyclinE expression; the opposite results were observed in the IL28RA-overexpressing HaCaT cells. Finally, a mechanistic study revealed that IL28RA functions through the activation of the Janus kinase-signal transducer and activator of transcription signaling pathway to exert its anti-proliferative effect. These results suggested that weak expression of IL28RA may contribute to the pathogenesis of psoriasis and that IL28RA may be an effective drug target for the treatment of psoriasis. However, further in vivo studies are required.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Psoríase / Queratinócitos / Receptores de Citocinas Limite: Adulto / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Mol Biol Rep Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China