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

Abstract

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.

• Authors: Philippe A Grange, Joël Raingeaud, Vincent Calvez, Nicolas Dupin
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 56 Issue 2 Pg. 106-12 (Nov 2009) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 19726162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• CXCL8 protein, human
• Dermatologic Agents
• I-kappa B Proteins
• Interleukin-8
• NF-kappa B
• RNA, Messenger
• Niacinamide
• Extracellular Signal-Regulated MAP Kinases
• JNK Mitogen-Activated Protein Kinases

Topics

• 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, 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)
• Phosphorylation
• Promoter Regions, Genetic (drug effects)
• Propionibacterium acnes (pathogenicity)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Transcriptional Activation (drug effects)
• Transfection