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Open AccessArticle

Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage

1
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand
3
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
4
School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia
5
Department of Medicine and Microbiology, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
6
VA Medical Center, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9374; https://doi.org/10.3390/ijms21249374
Received: 13 November 2020 / Revised: 4 December 2020 / Accepted: 6 December 2020 / Published: 9 December 2020
Lumisterol (L3) is a stereoisomer of 7-dehydrocholesterol and is produced through the photochemical transformation of 7-dehydrocholesteol induced by high doses of UVB. L3 is enzymatically hydroxylated by CYP11A1, producing 20(OH)L3, 22(OH)L3, 20,22(OH)2L3, and 24(OH)L3. Hydroxylumisterols function as reverse agonists of the retinoic acid-related orphan receptors α and γ (RORα/γ) and can interact with the non-genomic binding site of the vitamin D receptor (VDR). These intracellular receptors are mediators of photoprotection and anti-inflammatory activity. In this study, we show that L3-hydroxyderivatives significantly increase the expression of VDR at the mRNA and protein levels in keratinocytes, both non-irradiated and after UVB irradiation. L3-hydroxyderivatives also altered mRNA and protein levels for RORα/γ in non-irradiated cells, while the expression was significantly decreased in UVB-irradiated cells. In UVB-irradiated keratinocytes, L3-hydroxyderivatives inhibited nuclear translocation of NFκB p65 by enhancing levels of IκBα in the cytosol. This anti-inflammatory activity mediated by L3-hydroxyderivatives through suppression of NFκB signaling resulted in the inhibition of the expression of UVB-induced inflammatory cytokines, including IL-17, IFN-γ, and TNF-α. The L3-hydroxyderivatives promoted differentiation of UVB-irradiated keratinocytes as determined from upregulation of the expression at the mRNA of involucrin (IVL), filaggrine (FLG), and keratin 14 (KRT14), downregulation of transglutaminase 1 (TGM1), keratins including KRT1, and KRT10, and stimulation of ILV expression at the protein level. We conclude that CYP11A1-derived hydroxylumisterols are promising photoprotective agents capable of suppressing UVB-induced inflammatory responses and restoring epidermal function through targeting the VDR and RORs. View Full-Text
Keywords: photobiology; UV radiation; keratinocyte; inflammation; cell differentiation; lumisterol hydroxyderivatives photobiology; UV radiation; keratinocyte; inflammation; cell differentiation; lumisterol hydroxyderivatives
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MDPI and ACS Style

Chaiprasongsuk, A.; Janjetovic, Z.; Kim, T.-K.; Schwartz, C.J.; Tuckey, R.C.; Tang, E.K.Y.; Raman, C.; Panich, U.; Slominski, A.T. Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage. Int. J. Mol. Sci. 2020, 21, 9374. https://doi.org/10.3390/ijms21249374

AMA Style

Chaiprasongsuk A, Janjetovic Z, Kim T-K, Schwartz CJ, Tuckey RC, Tang EKY, Raman C, Panich U, Slominski AT. Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage. International Journal of Molecular Sciences. 2020; 21(24):9374. https://doi.org/10.3390/ijms21249374

Chicago/Turabian Style

Chaiprasongsuk, Anyamanee; Janjetovic, Zorica; Kim, Tae-Kang; Schwartz, Cynthia J.; Tuckey, Robert C.; Tang, Edith K.Y.; Raman, Chander; Panich, Uraiwan; Slominski, Andrzej T. 2020. "Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage" Int. J. Mol. Sci. 21, no. 24: 9374. https://doi.org/10.3390/ijms21249374

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