Nicotinamide inhibits Propionibacterium acnes-induced IL-8 production in keratinocytes through the NF-kappaB and MAPK pathways

• Published in: Journal of dermatological science 2009-11, Vol.56 (2), p.106-112
• Main Authors: Grange, Philippe A, Raingeaud, Joël, Calvez, Vincent, Dupin, Nicolas
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - pharmacology; Blotting, Western; Cell Line; Dermatologic Agents - pharmacology; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases - metabolism; Humans; I-kappa B Proteins - metabolism; Immunity, Innate - drug effects; Interleukin-8 - genetics; Interleukin-8 - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Keratinocytes - drug effects; Keratinocytes - enzymology; Keratinocytes - immunology; Keratinocytes - microbiology; MAP Kinase Signaling System - drug effects; NF-kappa B - metabolism; Niacinamide - pharmacology; Phosphorylation; Promoter Regions, Genetic - drug effects; Propionibacterium acnes - pathogenicity; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Time Factors; Transcriptional Activation - drug effects; Transfection
• ISSN: 1873-569X
• DOI: 10.1016/j.jdermsci.2009.08.001

Propionibacterium acnes (P. acnes) has been implicated in the inflammatory phase of acne vulgaris. It has been shown to activate interleukin-8 (IL-8) secretion by interacting with Toll-like receptor 2 (TLR-2) on the surface of keratinocytes. Nicotinamide has been shown to be an effective treatment for skin inflammation in various conditions, including acne vulgaris. To investigate the molecular mechanisms underlying the anti-inflammatory properties of nicotinamide in keratinocytes stimulated by P. acnes. HaCaT cells and primary keratinocyte cell lines were stimulated by P. acnes in the presence of nicotinamide. IL-8 production was monitored by ELISA on the cell culture supernatant and by qRT-PCR on total RNA extract. A luciferase reporter system assay was used to assess nicotinamide activity with the IL-8 promoter in transfected keratinocytes. We used western blotting to analyze the effect of nicotinamide on activation of the NF-kappaB and MAPK pathways. Nicotinamide significantly decreased IL-8 production in a dose-dependent manner, decreasing both mRNA and protein levels for this chemokine in immortalized HaCaT cells and primary keratinocytes. P. acnes-induced IL-8 promoter activation seemed to be downregulated by nicotinamide, which inhibited IkappaB degradation and the phosphorylation of ERK and JNK MAP kinases. Our results indicate that nicotinamide inhibits IL-8 production through the NF-kappaB and MAPK pathways in an in vitro keratinocytes/P. acnes model of inflammation. Keratinocytes involved in the innate immune response may be a suitable target for treatment during the early phase of inflammation.