title: Topical atorvastatin ameliorates 12-O-tetradecanoylphorbol-13-acetate induced skin inflammation by reducing cutaneous cytokine levels and NF-κB activation.
abstract: Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor used in the treatment of atherosclerosis and dyslipidemia. Studies have evaluated the utility of statins in the treatment of skin inflammation but with varied results. In the present study, we investigated the effect of atorvastatin on TNF-α release and keratinocyte proliferation in vitro and in acute and chronic 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation in vivo. Atorvastatin significantly inhibited lipopolysacharide induced TNF-α release in THP-1 cells and keratinocyte proliferation in HaCaT cells. In an acute study, topical atorvastatin showed dose dependent reduction in TPA induced skin inflammation with highest efficacy observed at 500 µg/ear dose. In chronic study, topical atorvastatin significantly reduced TPA induced ear thickness, ear weight, cutaneous cytokines, MPO activity and improved histopathological features comparable to that of dexamethasone. Atorvastatin also inhibited TPA stimulated NF-κB activation in mouse ear. In conclusion, our results suggest that atorvastatin ameliorates TPA induced skin inflammation in mice at least in part, due to inhibition of cytokine release and NF-κB activation and may be beneficial for the treatment skin inflammation like psoriasis.
authors.affiliation: Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Old Mahabalipuram Road, Shozhanganallur, Chennai, 600119, India.
authors.forename: Nagaraj M
authors.initials: NM
authors.lastname: Kulkarni
authors.forename: Milind M
authors.initials: MM
authors.lastname: Muley
authors.forename: Mallikarjun S
authors.initials: MS
authors.lastname: Jaji
authors.forename: G
authors.initials: G
authors.lastname: Vijaykanth
authors.forename: J
authors.initials: J
authors.lastname: Raghul
authors.forename: Neetin Kumar D
authors.initials: NK
authors.lastname: Reddy
authors.forename: Santosh L
authors.initials: SL
authors.lastname: Vishwakarma
authors.forename: Navin B
authors.initials: NB
authors.lastname: Rajesh
authors.forename: Jeyamurugan
authors.initials: J
authors.lastname: Mookkan
authors.forename: Uma Maheswari
authors.initials: UM
authors.lastname: Krishnan
authors.forename: Shridhar
authors.initials: S
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D003872:Dermatitis / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D000069059:Atorvastatin; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate