Publication: Hydroxylumisterols, photoproducts of pre-vitamin d3, protect human keratinocytes against uvb-induced damage
Issued Date
2020-12-02
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ISSN
14220067
16616596
16616596
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2-s2.0-85097521379
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Mahidol University
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SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences. Vol.21, No.24 (2020), 1-18
Suggested Citation
Anyamanee Chaiprasongsuk, Zorica Janjetovic, Tae Kang Kim, Cynthia J. Schwartz, Robert C. Tuckey, Edith K.Y. Tang, Chander Raman, Uraiwan Panich, Andrzej T. Slominski Hydroxylumisterols, photoproducts of pre-vitamin d3, protect human keratinocytes against uvb-induced damage. International Journal of Molecular Sciences. Vol.21, No.24 (2020), 1-18. doi:10.3390/ijms21249374 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/60385
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Title
Hydroxylumisterols, photoproducts of pre-vitamin d3, protect human keratinocytes against uvb-induced damage
Abstract
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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.