Maresin-1 suppresses imiquimod-induced skin inflammation by regulating IL-23 receptor expression

Sci Rep. 2018 Apr 3;8(1):5522. doi: 10.1038/s41598-018-23623-9.

Abstract

The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation. Topical MaR1 reduced the ear swelling response as seen in histological findings. RT-PCR and flow cytometry analyses revealed MaR1 had no inhibitory effect on IL-23, but MaR1 suppressed IL-17A production by γδTCRmid+ and CD4+ cells in the skin. These inhibitory effects were also observed in a subcutaneous IL-23-injected psoriasis model. MaR1 downmodulated IL-23 receptor (IL-23R) expression by suppressing retinoic acid-related orphan receptor γt (RORγt) expression and internalization in a clathrin-dependent manner in γδTCRmid+ and CD4+ cells. These results lead to assumptions that topical MaR1 may be a new therapeutic agent for psoriasis and other IL-17-mediated cutaneous inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Docosahexaenoic Acids / therapeutic use
  • Gene Expression Regulation / drug effects*
  • Imiquimod / pharmacology*
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Interleukin-17 / biosynthesis
  • Intraepithelial Lymphocytes / drug effects
  • Intraepithelial Lymphocytes / metabolism
  • Mice
  • Receptors, Interleukin / metabolism*
  • Skin / drug effects*
  • Skin / immunology
  • Skin / metabolism

Substances

  • 7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid
  • Interleukin-17
  • Receptors, Interleukin
  • interleukin-23 receptor, mouse
  • Docosahexaenoic Acids
  • Imiquimod