Inhibiting Sphingosine Kinase 2 Derived-sphingosine-1-phosphate Ameliorates Psoriasis-like Skin Disease via Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes in Mice

Acta Dermato-Venereologica

Sun-Hye Shin¹  So-Youn Woo²  Kyung-Ha Ryu²  Yu-He Kim²  Younghay Lee²  Soojung Hahn²  Kyung-Ah Cho²  Woo-Jae Park²  Joo-Won Park² 

[1] Department of Biochemistry, School of medicine, Ewha Womans University, 07985 Seoul, Korea. ;;

关键词: psoriasis;    CD4+ T lymphocyte;    sphingosine kinase;    sphingosine-1-phosphate;    Th17 differentiation;   

DOI  :  10.2340/00015555-3160

来源: DOAJ

【 摘 要 】

Sphingosine-1-phosphate (S1P) is a signalling sphingolipid metabolite that regulates important cell processes, including cell proliferation and apoptosis. Circulating S1P levels have been reported to be increased in patients with psoriasis relative to healthy patients. The aim of this study was to examine the potency of S1P inhibition using an imiquimod-induced psoriasis mouse model. Both topical ceramidase and sphingosine kinase 1/2 inhibition, which blocks S1P generation, alleviated imiquimod-induced skin lesions and reduced the serum interleukin 17-A levels induced by application of imiquimod. These treatments also normalized skin mRNA levels of genes associated with inflammation and keratinocyte differentiation. Inhibition of sphingosine kinase 2, but not sphingosine kinase 1, diminished levels of suppressor of cytokine signalling 1 and blocked T helper type 17 differentiation of naïve CD4+ T cells; imiquimod-induced psoriasis-like skin symptoms were also ameliorated. These results indicate the distinct effects of sphingosine kinase 1 and sphingosine kinase 2 inhibition on T helper type 17 generation and suggest molecules that inhibit S1P formation, including ceramidase and sphingosine kinase 2 inhibitors, as novel therapeutic candidates for psoriasis.

【 授权许可】

Unknown