Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin

PLoS Pathogens

Joël Raingeaud¹  Carole Nicco²  Bernard Weill³  Nicolas Dupin³  Christiane Chéreau³  Philippe A. Grange⁴  Frédéric Batteux⁴ 

[1] ERTi «Plateforme d'étude du stress oxydant en oncologie et dans les maladies inflammatoires», Faculté de Médecine, Université Paris Descartes, Paris, France;INSERM U749, Université Paris-sud, Faculté de Pharmacie, Chatenay-Malabry, France;Laboratoire d'Immunologie EA 1833, Faculté de Médecine, Université Paris Descartes, Paris, France;Laboratoire de Recherche en Dermatologie, EA 1833, Faculté de Médecine, Université Paris Descartes, Paris, France

关键词: Keratinocytes;    Anions;    Superoxides;    Acne;    Nitric oxide;    Inflammation;    Apoptosis;    Toll-like receptors;   

DOI  :  10.1371/journal.ppat.1000527

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY