Production of superoxide anions by keratinocytes initiates P. acnes-induced inflammation of the skin.
Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. Propionibacterium acnes (P. acnes), a gram-positive anareobic bacterium, plays a critical role in the development of these inflammatory lesions. This study aimed at determining whether reactive oxygen species (ROS) are produced by keratinocytes upon P. acnes infection, dissecting the mechanism of this production, and investigating how this phenomenon integrates in the general inflammatory response induced by P. acnes. In our hands, ROS, and especially superoxide anions (O2(*-)), were rapidly produced by keratinocytes upon stimulation by P. acnes surface proteins. In P. acnes-stimulated keratinocytes, O2(*-) was produced by NAD(P)H oxidase through activation of the scavenger receptor CD36. O2(*-) was dismuted by superoxide dismutase to form hydrogen peroxide which was further detoxified into water by the GSH/GPx system. In addition, P. acnes-induced O2(*-) abrogated P. acnes growth and was involved in keratinocyte lysis through the combination of O2(*-) with nitric oxide to form peroxynitrites. Finally, retinoic acid derivates, the most efficient anti-acneic drugs, prevent O2(*-) production, IL-8 release and keratinocyte apoptosis, suggesting the relevance of this pathway in humans.
Grange
Philippe A
PA
Laboratoire de Recherche en Dermatologie, EA 1833, Faculté de Médecine, Université Paris Descartes, Paris, France.
Chéreau
Christiane
C
Raingeaud
Joël
J
Nicco
Carole
C
Weill
Bernard
B
Dupin
Nicolas
N
Batteux
Frédéric
F
D000152:Acne Vulgaris / Q000378:metabolism* / Q000382:microbiology; D017209:Apoptosis; D018955:CD36 Antigens / Q000378:metabolism; D002461:Cell Line, Transformed; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000382:microbiology; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011425:Propionibacterium acnes / Q000254:growth & development / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D018955:CD36 Antigens; D016209:Interleukin-8; D009573:Nitrites; D017382:Reactive Oxygen Species; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases