Increased expression of heat shock protein 90 in keratinocytes and mast cells in patients with psoriasis

J Am Acad Dermatol. 2014 Apr;70(4):683-690.e1. doi: 10.1016/j.jaad.2013.12.002. Epub 2014 Feb 9.

Abstract

Background: Psoriasis is a chronic inflammatory skin disease and various stress factors mediate inflammation. Heat shock protein (HSP) 90 plays an important role in cell survival; cytokine signaling, such as interleukin-17 receptor signaling; and immune responses.

Objective: We sought to elucidate protein expression and distribution of HSP90 in psoriasis.

Methods: HSP90 expression and its cellular source were analyzed on normal-appearing, nonlesional, lesional, and ustekinumab-treated psoriatic skin using immunohistochemistry and double immunofluorescence.

Results: HSP90α, the inducible isoform of HSP90, was significantly up-regulated in epidermal keratinocytes and mast cells of lesional skin and down-regulated after ustekinumab therapy.

Limitations: There was a limited sample size.

Conclusions: HSP90 from keratinocytes and mast cells is a key regulator of psoriatic inflammation and HSP90 inhibitors may represent a novel therapeutic approach to the disease.

Keywords: heat shock protein; heat shock protein 90; heat shock protein 90 inhibitor; keratinocytes; mast cells; psoriasis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Case-Control Studies
  • Cohort Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation*
  • HSP90 Heat-Shock Proteins / drug effects
  • HSP90 Heat-Shock Proteins / genetics*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Male
  • Mast Cells / cytology
  • Mast Cells / metabolism
  • Middle Aged
  • Molecular Targeted Therapy
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Psoriasis / pathology
  • RNA, Messenger / analysis
  • Reference Values
  • Risk Assessment
  • Statistics, Nonparametric
  • Treatment Outcome
  • Up-Regulation
  • Ustekinumab

Substances

  • Antibodies, Monoclonal, Humanized
  • HSP90 Heat-Shock Proteins
  • RNA, Messenger
  • Ustekinumab