title: Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner.
abstract: It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1.
authors: Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, Kangwon National University School of Medicine, Chuncheon 200-701, Korea.
authors: Mi Eun
authors: ME
authors: Lee
authors: So Ra
authors: SR
authors: Kim
authors: Seungkoo
authors: S
authors: Lee
authors: Yu-Jin
authors: YJ
authors: Jung
authors: Sun Shim
authors: SS
authors: Choi
authors: Woo Jin
authors: WJ
authors: Kim
authors: Jeong A
authors: JA
authors: Han
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D002384:Catalysis; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D000068579:Celecoxib; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D051379:Mice; D009578:Nitrobenzenes / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage; D015595:Skin Aging / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D024042:Collagen Type I; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D001241:Aspirin