Heat-shock pretreatment reduces expression and release of TSLP from keratinocytes under Th2 environment

Pediatr Allergy Immunol. 2016 Feb;27(1):62-9. doi: 10.1111/pai.12482. Epub 2015 Sep 30.

Abstract

Background: Atopic dermatitis is a chronic, relapsing inflammatory disease of the skin. Current therapy is not curative, and recalcitrant disease is a big stress and challenge for parents and physicians. This study explored the potential role of heat-shock protein 70 (HSP-70) and its anti-inflammatory effects on keratinocyte under TH2 environment.

Methods: Human keratinocyte cell line (HaCa T) was stimulated with IL-4, IL-13, and TNF-α to synthesize and secrete thymic stromal lymphopoietin (TSLP), an important cytokine of immunopathogenesis in atopic dermatitis. Heat shock was performed by immersing the cell-contained flash into a water bath of 45°C for 20 min. Cell viability, TSLP expression, and secretion of HaCa T cells were measured and compared. Possible regulatory mechanisms influencing the expression of TSLP, such as the STAT6 and NF-κB signal pathways, were investigated.

Results: Heat-shock treatment induced intracellular HSP-70 expression in HaCa T cells without affecting cell viability. The induced expression and secretion of TSLP in HaCa T cells were suppressed by heat shock. The NF-κB signal pathway was inhibited by heat shock, leading to decreased TSLP expression and secretion.

Conclusion: Heat stress-induced HSPs can significantly reduce the production and secretion of TSLP from HaCaT cells under Th2 environment. Thus, the evidence highlights the potential role of HSP-70 for atopic dermatitis in the future.

Keywords: atopic dermatitis; heat shock; heat-shock protein; thymic stromal lymphopoietin.

MeSH terms

  • Cell Line
  • Cellular Microenvironment*
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism*
  • Dermatitis, Atopic / prevention & control
  • Down-Regulation
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Response*
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • NF-kappa B / metabolism
  • Signal Transduction
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*
  • Thymic Stromal Lymphopoietin
  • Time Factors
  • Transcription, Genetic

Substances

  • Cytokines
  • HSP70 Heat-Shock Proteins
  • Inflammation Mediators
  • NF-kappa B
  • Thymic Stromal Lymphopoietin