Brevilin A inhibits IL‑17A‑induced inflammation in psoriasis by modulating HSP 70

Mol Med Rep. 2025 Jun;31(6):156. doi: 10.3892/mmr.2025.13521. Epub 2025 Apr 11.

Abstract

Psoriasis, which is characterized by keratinocyte hyperproliferation, presents complex management challenges. The heat shock protein 70 (HSP 70) family, which is essential in protein folding and stress responses, also modulates inflammation, suggesting its therapeutic potential in inflammation‑driven diseases. The present study aimed to explore the effects of brevilin A, a natural compound known to alleviate imiquimod‑induced psoriasis, on HSP 70 expression and proinflammatory cytokine production in HaCaT cells stimulated with IL‑17A. An HSP 70 inhibitor was used to determine its role in cytokine regulation, and the effect of brevilin A on skin pathology in mice was examined via immunohistochemistry and hematoxylin and eosin staining. The results revealed that brevilin A markedly decreased IL‑6 and IL‑8 levels after IL‑17A stimulation at both 9 and 24 h in HaCaT cells, and increased HSP 70 and HSP 90 expression levels. Notably, the brevilin A‑induced suppression of cytokine levels was reversed when cells were co‑treated with the HSP 70 inhibitor. In vivo, brevilin A enhanced HSP 70 expression and reduced skin hyperproliferation. These findings suggested that brevilin A may modulate HSP 70 expression and dampen the inflammatory response induced by IL‑17A, indicating its potential as an innovative treatment for psoriasis.

Keywords: IL‑17A; heat shock protein 70; keratinocytes; psoriasis.

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / metabolism
  • Disease Models, Animal
  • HSP70 Heat-Shock Proteins* / genetics
  • HSP70 Heat-Shock Proteins* / metabolism
  • HaCaT Cells
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Interleukin-17* / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Psoriasis* / chemically induced
  • Psoriasis* / drug therapy
  • Psoriasis* / metabolism
  • Psoriasis* / pathology
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology

Substances

  • Interleukin-17
  • HSP70 Heat-Shock Proteins
  • Cytokines