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

Title
Inhibiting Sphingosine Kinase 2 Derived-sphingosine-1-phosphate Ameliorates Psoriasis-like Skin Disease via Blocking Th17 Differentiation of Naive CD4 T Lymphocytes in Mice
Authors
Shin, Sun-HyeCho, Kyung-AhHahn, SoojungLee, YounghayKim, Yu-HeeWoo, So-YounRyu, Kyung-HaPark, Woo-JaePark, Joo-Won
Ewha Authors
유경하우소연박주원
SCOPUS Author ID
유경하scopus; 우소연scopus; 박주원scopus
Issue Date
2019
Journal Title
ACTA DERMATO-VENEREOLOGICA
ISSN
0001-5555JCR Link

1651-2057JCR Link
Citation
ACTA DERMATO-VENEREOLOGICA vol. 99, no. 6, pp. 594 - 601
Keywords
psoriasisCD4(+) T lymphocytesphingosine kinasesphingosine-1-phosphateTh17 differentiation
Publisher
ACTA DERMATO-VENEREOLOGICA
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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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DOI
10.2340/00015555-3160
Appears in Collections:
의과대학 > 의학과 > Journal papers
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