Anyamanee ChaiprasongsukZorica JanjetovicTae Kang KimRobert C. TuckeyWei LiChander RamanUraiwan PanichAndrzej T. SlominskiBirmingham VA Medical CenterUniversity of Western AustraliaThe University of Alabama at BirminghamFaculty of Medicine, Siriraj Hospital, Mahidol UniversityUniversity of Tennessee Health Science CenterChulabhorn Royal Academy2020-08-252020-08-252020-08-01Free Radical Biology and Medicine. Vol.155, (2020), 87-9818734596089158492-s2.0-85085659986https://repository.li.mahidol.ac.th/handle/123456789/57695© 2020 UVB radiation mediates inflammatory responses causing skin damage and defects in epidermal differentiation. 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) interacts with the vitamin D3 receptor (VDR) to regulate inflammatory responses. Additionally, 1,25(OH)2D3/VDR signaling represents a potential therapeutic target in the treatment of skin disorders associated with inflammation and poor differentiation of keratinocytes. Since the protective effect of 1,25(OH)2D3 against UVB-induced skin damage and inflammation is recognized, CYP11A1-derived vitamin D3-hydroxyderivatives including 20(OH)D3, 1,20(OH)2D3, 20,23(OH)2D3 and 1,20,23(OH)3D3 were tested for their anti-inflammatory and skin protection properties in UVB-irradiated human epidermal keratinocytes (HEKn). HEKn were treated with secosteroids for 24 h pre- and post-UVB (50 mJ/cm2) irradiation. Secosteroids modulated the expression of the inflammatory response genes (IL-17, NF-κB p65, and IκB-α), reducing nuclear-NF-κB-p65 activity and increasing cytosolic-IκB-α expression as well as that of pro-inflammatory mediators, IL-17, TNF-α, and IFN-γ. They stimulated the expression of involucrin (IVL) and cytokeratin 10 (CK10), the major markers of epidermal differentiation, in UVB-irradiated cells. We conclude that CYP11A1-derived hydroxyderivatives inhibit UVB-induced epidermal inflammatory responses through activation of IκB-α expression and suppression of NF-kB-p65 activity and its downstream signaling cytokines, TNF-α, and IFN-γ, as well as by inhibiting IL-17 production and activating epidermal differentiation.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1016/j.freeradbiomed.2020.05.016