Heat shock protein 90 is involved in IL-17-mediated skin inflammation following thermal stimulation

Int J Mol Med. 2016 Aug;38(2):650-8. doi: 10.3892/ijmm.2016.2627. Epub 2016 Jun 7.

Abstract

The pathogenesis of inflammatory skin diseases involves interactions between immune cells and keratinocytes, including the T helper 17 (Th17)-mediated immune response. Several chemokines [chemokine (C-X-C motif) ligand (CXCL)1, CXCL5 and CXCL8] and antimicrobial peptides [β-defensin 1 (BD1), LL-37, S100A8 and S100A9] were transcriptionally upregulated in the keratinocyte cell line HaCaT upon stimulation with interleukin (IL)-17. Balneotherapy, the treatment of disease by bathing, is an alternative therapy that has frequently been used for the treatment of inflammatory skin diseases. Immersion in pools of thermal mineral water is often considered to have chemical, thermal, mechanical and immunomodulatory benefits. We examined the effect of thermal treatment on IL-17-mediated inflammation in a model of skin disease. As Act1 is required for IL-17 signaling and is a client protein of heat shock protein 90 (HSP90), we evaluated the effect of HSP90 inhibition on IL-17-mediated cytokine and antimicrobial peptide expression in keratinocytes following heat treatment. We found that after thermal stimulation, Act1 binding to HSP90α was significantly increased in the presence of IL-17 (100 ng/ml) and 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, 1 µM). Antimicrobial peptide and chemokine expression generally increased after heat treatment; Act1 knockdown and 17‑AAG reversed this effect. These observations demonstrate the possible immunomodulatory effect of heat on keratinocytes during the progression of IL-17-mediated inflammatory skin diseases.

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism
  • Benzoquinones
  • Cell Line
  • Connexin 43 / metabolism
  • Gene Knockdown Techniques
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Interleukin-17 / metabolism*
  • Interleukin-1beta / metabolism
  • Lactams, Macrocyclic
  • Peptide Fragments / metabolism
  • Protein Binding
  • RNA, Small Interfering / metabolism
  • Skin / pathology*
  • Temperature*

Substances

  • ACT1 protein
  • Antimicrobial Cationic Peptides
  • Benzoquinones
  • Connexin 43
  • HSP90 Heat-Shock Proteins
  • Interleukin-17
  • Interleukin-1beta
  • Lactams, Macrocyclic
  • Peptide Fragments
  • RNA, Small Interfering
  • tanespimycin