Piceatannol Inhibits P. acnes-Induced Keratinocyte Proliferation and Migration by Downregulating Oxidative Stress and the Inflammatory Response

Inflammation. 2020 Feb;43(1):347-357. doi: 10.1007/s10753-019-01125-8.

Abstract

The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3', 4'-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.

Keywords: Piceatannol; Propionibacterium acnes; acne vulgaris; anti-inflammation; nuclear factor erythroid 2-related factor 2.

MeSH terms

  • Acne Vulgaris / metabolism
  • Acne Vulgaris / microbiology
  • Acne Vulgaris / pathology
  • Acne Vulgaris / prevention & control*
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Line
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / metabolism*
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / microbiology
  • Keratinocytes / pathology
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Propionibacterium acnes / pathogenicity
  • Signal Transduction
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / microbiology
  • Skin / pathology
  • Stilbenes / pharmacology*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • RELA protein, human
  • Stilbenes
  • Transcription Factor RelA
  • 3,3',4,5'-tetrahydroxystilbene