7-Hydroxycoumarin prevents UVB-induced activation of NF-κB and subsequent overexpression of matrix metalloproteinases and inflammatory markers in human dermal fibroblast cells

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2016-08, Vol.161, p.170-176
• Main Authors: Karthikeyan, Ramasamy, Kanimozhi, Govindasamy, Prasad, Nagarajan Rajendra, Agilan, Balupillai, Ganesan, Muthusamy, Mohana, Shanmugham, Srithar, Gunaseelan
• Format: Article
• Language: English
• Subjects: 7-Hydroxycoumarin; Antioxidants - metabolism; Cell Survival - drug effects; Cell Survival - radiation effects; Cells, Cultured; Cyclooxygenase 2 - metabolism; DNA Damage - drug effects; DNA Damage - radiation effects; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Inflammation; Interleukin-6 - metabolism; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; NF-kappa B - metabolism; Oxidative Stress - drug effects; Oxidative Stress - radiation effects; Photoaging; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; Sun Protection Factor; Tumor Necrosis Factor-alpha - metabolism; Ultraviolet Rays; Umbelliferones - pharmacology; UVB radiation
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2016.04.027

Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage. Human dermal fibroblasts (HDFa) were subjected to single UVB-irradiation (18mJ/cm2) resulting in reactive oxygen species (ROS) generation, oxidative DNA damage and upregulation of nuclear factor kappa B (NF-κB) expression. Further, it has been observed that there was a significant cytokine production (TNF-α and IL-6) in UVB irradiated HDFa cells. Our results show that 7-hydroxycoumarin (7-OHC) prevents UVB-induced activation of NF-κB thereby subsequently preventing the overexpression of TNF-α and IL-6 in HDFa cells. Further, 7-OHC prevents UVB-induced activation of cyclooxygenase-2 (COX-2) expression, an inflammatory mediator in skin cells. Moreover, 7-OHC inhibited mRNA expression pattern of matrix metalloproteinases (MMP-1 and MMP-9) in UVB irradiated skin cells. Furthermore, 7-OHC restored antioxidant status, thereby scavenging the excessively generated ROS; consequently preventing the oxidative DNA damage. It has also been noticed that 7-OHC prevents UVB mediated DNA damage through activation of DNA repair enzymes such as XRCC1 and HOGG1. In this study, we treated HDFa cells with 7-OHC before and after UVB irradiation and we found that pretreatment showed better results when compared to posttreatment. Further, 7-OHC showed 9.8416 sun protection factor (SPF) value and it absorbs photons in the UVB wavelength rage. Thus, it has been concluded that sunscreen property, free radical scavenging potential and prevention of NF-κB activation play a role for photoprotective property of 7-OHC. [Display omitted] •7-OHC prevents the activation of NF-κB thereby prevent UVB mediated inflammation and photo-damage.•Antioxidant property of 7-OHC prevents UVB induced oxidative DNA damage.•7-OHC protects against UVB-irradiation by acting as sun screen.