Topical application of glycolic acid suppresses the UVB induced IL-6, IL-8, MCP-1 and COX-2 inflammation by modulating NF-κB signaling pathway in keratinocytes and mice skin

J Dermatol Sci. 2017 Jun;86(3):238-248. doi: 10.1016/j.jdermsci.2017.03.004. Epub 2017 Mar 11.

Abstract

Background: Glycolic acid (GA), commonly present in fruits, has been used to treat dermatological diseases. Extensive exposure to solar ultraviolet B (UVB) irradiation plays a crucial role in the induction of skin inflammation. The development of photo prevention from natural materials represents an effective strategy for skin keratinocytes.

Objective: The aim of this study was to investigate the molecular mechanisms underlying the glycolic acid (GA)-induced reduction of UVB-mediated inflammatory responses.

Methods: We determined the effects of different concentrations of GA on the inflammatory response of human keratinocytes HaCaT cells and C57BL/6J mice dorsal skin. After GA was topically applied, HaCaT and mice skin were exposed to UVB irradiation.

Results: GA reduced the production of UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators [interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP-1)] at both mRNA and protein levels. GA inhibited the UVB-induced promoter activity of NF-κB in HaCaT cells. GA attenuated the elevation of senescence associated with β-galactosidase activity but did not affect the wound migration ability. The topical application of GA inhibited the genes expression of IL-1β, IL-6, IL-8, COX-2, and MCP-1 in UVB-exposed mouse skin. The mice to UVB irradiation after GA was topically applied for 9 consecutive days and reported that 1-1.5% of GA exerted anti-inflammatory effects on mouse skin.

Conclusion: We clarified the molecular mechanism of GA protection against UVB-induced inflammation by modulating NF-κB signaling pathways and determined the optimal concentration of GA in mice skin exposed to UVB irradiation.

Keywords: Glycolic acid (GA); cyclooxygenase (COX)-2; interleukin (IL)-1β; monocyte chemoattractant protein (MCP-1); nuclear factor kappa B (NF-κB); ultraviolet B (UVB).

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / radiation effects
  • Cellular Senescence / drug effects
  • Cellular Senescence / radiation effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Chemokine CCL2 / metabolism*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology
  • Cyclooxygenase 2 / metabolism*
  • Dose-Response Relationship, Drug
  • Glycolates / administration & dosage*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism*
  • Keratinocytes / drug effects*
  • Keratinocytes / enzymology
  • Keratinocytes / immunology
  • Keratinocytes / radiation effects*
  • Male
  • Mice, Inbred C57BL
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Skin / drug effects*
  • Skin / enzymology
  • Skin / immunology
  • Skin / radiation effects*
  • Time Factors
  • Transfection
  • Ultraviolet Rays*

Substances

  • Anti-Inflammatory Agents
  • CCL2 protein, human
  • CXCL8 protein, human
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Glycolates
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • RNA, Messenger
  • interleukin-6, mouse
  • glycolic acid
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • PTGS2 protein, human