Document Detail

Nicotinamide inhibits Propionibacterium acnes-induced IL-8 production in keratinocytes through the NF-kappaB and MAPK pathways.
MedLine Citation:
PMID:  19726162     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
Philippe A Grange; Jo??l Raingeaud; Vincent Calvez; Nicolas Dupin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-01
Journal Detail:
Title:  Journal of dermatological science     Volume:  56     ISSN:  1873-569X     ISO Abbreviation:  J. Dermatol. Sci.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-06     Completed Date:  2009-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9011485     Medline TA:  J Dermatol Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  106-12     Citation Subset:  IM    
H??pital Cochin - Pavillon Gustave Roussy, Universit?? Paris Descartes, UPRES-EA 1833, Laboratoire de Recherches en Dermatologie, 8, rue M??chain, 75014 Paris, France.
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MeSH Terms
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
I-kappa B Proteins / metabolism
Immunity, Innate / drug effects
Interleukin-8 / genetics,  metabolism*
JNK Mitogen-Activated Protein Kinases / metabolism
Keratinocytes / drug effects*,  enzymology,  immunology,  microbiology
MAP Kinase Signaling System / drug effects*
NF-kappa B / metabolism*
Niacinamide / pharmacology*
Promoter Regions, Genetic / drug effects
Propionibacterium acnes / pathogenicity*
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transcriptional Activation / drug effects
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Dermatologic Agents; 0/I-kappa B Proteins; 0/IL8 protein, human; 0/Interleukin-8; 0/NF-kappa B; 0/RNA, Messenger; 98-92-0/Niacinamide; EC Signal-Regulated MAP Kinases; EC Mitogen-Activated Protein Kinases

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