Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage
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 a...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9374 |
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| author | Anyamanee Chaiprasongsuk Zorica Janjetovic Tae-Kang Kim Cynthia J. Schwartz Robert C. Tuckey Edith K. Y. Tang Chander Raman Uraiwan Panich Andrzej T. Slominski |
| author_facet | Anyamanee Chaiprasongsuk Zorica Janjetovic Tae-Kang Kim Cynthia J. Schwartz Robert C. Tuckey Edith K. Y. Tang Chander Raman Uraiwan Panich Andrzej T. Slominski |
| author_sort | Anyamanee Chaiprasongsuk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:13:07Z |
| format | Article |
| id | doaj.art-dda599985b99499ba8b8accb57b2e6ac |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:13:07Z |
| publishDate | 2020-12-01 |
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| spelling | doaj.art-dda599985b99499ba8b8accb57b2e6ac2023-11-21T00:01:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124937410.3390/ijms21249374Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced DamageAnyamanee Chaiprasongsuk0Zorica Janjetovic1Tae-Kang Kim2Cynthia J. Schwartz3Robert C. Tuckey4Edith K. Y. Tang5Chander Raman6Uraiwan Panich7Andrzej T. Slominski8Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USASchool of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, AustraliaSchool of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, AustraliaDepartment of Medicine and Microbiology, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USALumisterol (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.https://www.mdpi.com/1422-0067/21/24/9374photobiologyUV radiationkeratinocyteinflammationcell differentiationlumisterol hydroxyderivatives |
| spellingShingle | 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 photobiology UV radiation keratinocyte inflammation cell differentiation lumisterol hydroxyderivatives |
| title | Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage |
| title_full | Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage |
| title_fullStr | Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage |
| title_full_unstemmed | Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage |
| title_short | Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage |
| title_sort | hydroxylumisterols photoproducts of pre vitamin d3 protect human keratinocytes against uvb induced damage |
| topic | photobiology UV radiation keratinocyte inflammation cell differentiation lumisterol hydroxyderivatives |
| url | https://www.mdpi.com/1422-0067/21/24/9374 |
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