5-hydroxytryptophan attenuates imiquimod-induced psoriasiform dermatitis probably through inhibition of IL-17A production and keratinocyte activation

Exp Dermatol. 2018 Nov;27(11):1273-1279. doi: 10.1111/exd.13781. Epub 2018 Oct 9.

Abstract

Psoriasis is a chronic autoimmune disease with keratinocyte activation and lymphocyte infiltration in the skin. Our previous study found that 5-hydroxytryptophan (5(OH)Trp), a tryptophan metabolite, alleviated collagen-induced arthritis and suppressed cytokine production. In this study, we evaluated the effects of 5(OH)Trp in a mouse model for psoriasiform dermatitis, induced by imiquimod (IMQ). We showed that 5(OH)Trp significantly reduced the cumulative scores, epidermal thickness and ki-67 expression in the skin. In addition, 5(OH)Trp decreased local and systemic inflammation. Moreover, 5(OH)Trp significantly inhibited keratinocyte activation with decrease in IL-6 production and p-Erk1/2 and p-STAT3 expression. 5(OH)Trp also inhibited the differentiation of IFN-γ- and IL-17A-expressing CD4+ T cells and related cytokine production (TNF-α, IL-6, IL-17A and IFN-γ) in splenocytes. In conclusion, 5(OH)Trp can inhibit imiquimod-induced psoriasiform dermatitis in mice and inhibit activation in keratinocytes and splenocytes.

Keywords: 5-hydroxytryptophan; IL-17A; imiquimod; psoriasiform dermatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / pharmacology
  • 5-Hydroxytryptophan / therapeutic use*
  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Epidermis / pathology
  • Humans
  • Imiquimod
  • Interferon-gamma / metabolism
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / metabolism
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / metabolism
  • Keratinocytes / physiology*
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Biosynthesis / drug effects
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / pathology
  • Spleen / cytology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • IL6 protein, human
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Ki-67 Antigen
  • Mki67 protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Interferon-gamma
  • 5-Hydroxytryptophan
  • Cyclooxygenase 2
  • Imiquimod