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


OBJECTIVE
To investigate the molecular mechanisms underlying the anti-inflammatory properties of nicotinamide in keratinocytes stimulated by P. acnes.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Grange
Philippe A
PA
Hôpital Cochin - Pavillon Gustave Roussy, Université Paris Descartes, UPRES-EA 1833, Laboratoire de Recherches en Dermatologie, 8, rue Méchain, 75014 Paris, France. philippe.grange@cch.aphp.fr
Raingeaud
Joël
J
Calvez
Vincent
V
Dupin
Nicolas
N
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D003879:Dermatologic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011425:Propionibacterium acnes / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D003879:Dermatologic Agents; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D009536:Niacinamide; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases