Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model

Kaohsiung J Med Sci. 2020 Mar;36(3):186-195. doi: 10.1002/kjm2.12163. Epub 2020 Jan 6.

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD. An experimental model of AD was reproduced by systemic sensitization and local epicutaneous challenge with ovalbumin (OVA). Treatment of rHSP70 was performed by subcutaneous administration. The levels of OVA-specific IgE, as well as cytokines, were detected by ELISA. Skin samples from patch areas were also taken for histologic examination. Injection of rHSP70 improved the histologic picture by reducing the thickness of epidermis and allergic inflammation. Skin sonography revealed rHSP70 ameliorated skin remodeling. rHSP70 also significantly decreased the protein expression of TSLP of skin from patch areas. Furthermore, in ex vivo studies also showed group of rHSP70 treatment decreased IL-13, RANTES, MIP-1β and increased IFN-γ secreted from splenocytes stimulated with OVA. The rHSP70 intervention in the mouse model of AD reduced the skin expression of TSLP and attenuated the clinical appearance of OVA-induced AD mice. The effect was achieved by suppressed Th2 immune response in injected skin tissue and enhanced systemic Th1 immune response. These results suggest that rHSP70 have potential as a promising protein for the treatment of AD.

Keywords: atopic dermatitis; heat shock protein; skin barrier; skin inflammation; thymic stromal lymphopoietin.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / metabolism
  • Disease Models, Animal
  • Epidermis / drug effects
  • Epidermis / metabolism
  • Female
  • HSP70 Heat-Shock Proteins / administration & dosage
  • HSP70 Heat-Shock Proteins / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Injections, Subcutaneous
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • HSP70 Heat-Shock Proteins
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse