Inhibiting Sphingosine Kinase 2 Derived-sphingosine-1-phosphate Ameliorates Psoriasis-like Skin Disease via Blocking Th17 Differentiation of Naive CD4 T Lymphocytes in Mice
- 주제(키워드) psoriasis , CD4(+) T lymphocyte , sphingosine kinase , sphingosine-1-phosphate , Th17 differentiation
- 주제(기타) Dermatology
- 설명문(일반) [Shin, Sun-Hye; Hahn, Soojung; Lee, Younghay; Park, Joo-Won] Ewha Womans Univ, Coll Med, Dept Biochem, Seoul 07985, South Korea; [Cho, Kyung-Ah; Kim, Yu-Hee; Woo, So-Youn] Ewha Womans Univ, Coll Med, Dept Microbiol, Seoul, South Korea; [Ryu, Kyung-Ha] Ewha Womans Univ, Coll Med, Dept Pediat, Seoul, South Korea; [Hahn, Soojung] Sungkyunkwan Univ, Grad Sch, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul, South Korea; [Park, Woo-Jae] Gachon Univ, Coll Med, Dept Biochem, Incheon 21999, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold
- 발행기관 ACTA DERMATO-VENEREOLOGICA
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159786
- 본문언어 영어
- Published As http://dx.doi.org/10.2340/00015555-3160
- PubMed https://pubmed.ncbi.nlm.nih.gov/30834454
초록/요약
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 naive 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.
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