Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARγ activation

Arianna Mastrofrancesco, Monica Ottaviani, Nicaela Aspite, Giorgia Cardinali, Enzo Izzo, Klaus Graupe, Christos C. Zouboulis, Emanuela Camera, Mauro Picardo

Research output: Contribution to journalArticle

Abstract

Azelaic acid (AzA), a nine-carbon dicarboxylic acid, is an agent for the topical treatment of acne. It has also been shown to be effective in rosacea; however, the mechanism of action has not been clarified. Because inflammation is a common feature of both conditions, we investigated the effects of azelaic acid on the inflammatory response of normal human keratinocytes to ultraviolet B light, which is a photosensitizer agent in rosacea. AzA, at 20 m. m, a concentration achievable following topical application of a 15% gel, suppresses ultraviolet B light-induced interleukins-1β, -6 and tumor necrosis factor-α mRNA expression and protein secretion. Mechanistically, azelaic acid significantly reduced the ultraviolet B light-induced nuclear translocation of nuclear factor kB p65 subunit and the phosphorylation of the p38 mitogen and stress-activated protein kinase. Moreover, as peroxisome proliferators-activated receptor γ, (PPARγ) which has a crucial role in the control of inflammation, is activated by fatty acids and products of lipid peroxidation, we further investigated the effect of azelaic acid on the expression of this nuclear receptor. AzA induced peroxisome proliferators-activated receptor-γ mRNA and its transcriptional activity. The PPARγ antagonist GW9662 abrogated the inhibitory effects of AzA on the UVB-induced pro-inflammatory cytokines release and on the cell proliferation. Our study provides new insights into the molecular mechanisms of the activity of azelaic acid and lands additional evidences for its therapeutic effects on inflammatory skin diseases, such as rosacea.

Original languageEnglish
Pages (from-to)813-820
Number of pages8
JournalExperimental Dermatology
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2010

Keywords

  • Azelaic acid
  • Inflammatory cytokines
  • PPARγ
  • Rosacea
  • UV

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

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