| First Author | Zhao S | Year | 2021 |
| Journal | J Invest Dermatol | Volume | 141 |
| Issue | 11 | Pages | 2699-2709.e2 |
| PubMed ID | 34051272 | Mgi Jnum | J:317282 |
| Mgi Id | MGI:6789607 | Doi | 10.1016/j.jid.2021.03.032 |
| Citation | Zhao S, et al. (2021) Bestatin Cream Impairs Solar Simulated LightDriven Skin Inflammation and Skin Carcinogenesis in Mice. J Invest Dermatol 141(11):2699-2709.e2 |
| abstractText | Leukotriene A4 hydrolase (LTA4H) is an enzyme that catalyzes the production of the inflammatory mediator leukotriene B4, which is involved in inflammatory responses mediated through the leukotriene B4/leukotriene B4 receptor type 1 (BLT1) signaling pathway. In this study, we investigated whether bestatin, an LTA4H inhibitor, could suppress skin acute inflammation and carcinogenesis. In the clinical sample, BLT1 was significantly induced in human skin tissues after acute solar simulated light (SSL) exposure. BLT1 and NF-kappaB p65 expressions were also increased in acute SSLinduced mouse skin tissue. Furthermore, LTA4H and BLT1 were highly expressed in skin chronic inflammation and squamous cell carcinomas. More importantly, topical administration of bestatin cream dramatically inhibited BLT1 expression in acute SSLinduced human skin tissues. BLT1 and NF-kappaB p65 expressions were also suppressed in acute SSLinduced Lta4h-knockout and bestatin-treated mice skin tissues. Moreover, we conducted long-term prevention and therapeutic studies, which showed that bestatin significantly attenuated SSL-induced skin carcinogenesis. Mechanistic studies showed that bestatin inhibited skin carcinogenesis by suppressing cell proliferation and inducing cell apoptosis through LTA4HBLT1protein kinase BNF-kappaB p65 pathway. Overall, our results suggest that topical application of novel cream containing bestatin might open a helpful avenue for SSL-induced skin carcinogenesis. |
