A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes
DC Field | Value | Language |
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dc.contributor.author | Shin, S.-H. | - |
dc.contributor.author | Kim, H.-Y. | - |
dc.contributor.author | Yoon, H.-S. | - |
dc.contributor.author | Park, W.-J. | - |
dc.contributor.author | Adams, D.R. | - |
dc.contributor.author | Pyne, N.J. | - |
dc.contributor.author | Pyne, S. | - |
dc.contributor.author | Park, J.-W. | - |
dc.date.available | 2020-11-30T00:41:13Z | - |
dc.date.created | 2020-11-20 | - |
dc.date.issued | 2020-11 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79105 | - |
dc.description.abstract | Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naïve CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | International journal of molecular sciences | - |
dc.title | A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000588956700001 | - |
dc.identifier.doi | 10.3390/ijms21218371 | - |
dc.identifier.bibliographicCitation | International journal of molecular sciences, v.21, no.21 | - |
dc.identifier.scopusid | 2-s2.0-85096030641 | - |
dc.citation.title | International journal of molecular sciences | - |
dc.citation.volume | 21 | - |
dc.citation.number | 21 | - |
dc.contributor.affiliatedAuthor | Park, W.-J. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | HWG-35D | - |
dc.subject.keywordAuthor | psoriasis | - |
dc.subject.keywordAuthor | sphingosine kinase | - |
dc.subject.keywordAuthor | sphingosine-1-phosphate | - |
dc.subject.keywordAuthor | T helper type 17 differentiation | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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