View : 445 Download: 0
A novel selective sphingosine kinase 2 inhibitor, hwg-35d, ameliorates the severity of imiquimod-induced psoriasis model by blocking th17 differentiation of naive cd4 t lymphocytes
- Title
- A novel selective sphingosine kinase 2 inhibitor, hwg-35d, ameliorates the severity of imiquimod-induced psoriasis model by blocking th17 differentiation of naive cd4 t lymphocytes
- Authors
- Shin S.-H.; Kim H.-Y.; Yoon H.-S.; Park W.-J.; Adams D.R.; Pyne N.J.; Pyne S.; Park J.-W.
- Ewha Authors
- 박주원
- SCOPUS Author ID
- 박주원
- Issue Date
- 2020
- Journal Title
- International Journal of Molecular Sciences
- ISSN
- 1661-6596
- Citation
- International Journal of Molecular Sciences vol. 21, no. 21, pp. 1 - 16
- Keywords
- HWG-35D; Psoriasis; Sphingosine kinase; Sphingosine-1-phosphate; T helper type 17 differentiation
- Publisher
- MDPI AG
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 naive 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. © 2020, MDPI AG. All rights reserved.
- DOI
- 10.3390/ijms21218371
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML