SIRT5 reduces the inflammatory response and barrier dysfunction in IL-17A-induced epidermal keratinocytes

Allergol Immunopathol (Madr). 2023 Jan 1;51(1):30-36. doi: 10.15586/aei.v51i1.675. eCollection 2023.

Abstract

Psoriasis is a chronic multisystemic inflammatory disease with inflammatory cell infiltration, hyperproliferation of keratinocytes in skin lesions, and epidermal barrier dysfunction. Normal human epidermal keratinocytes (NHEKs) were stimulated with interleukin 17A (IL-17A). The expression levels of sirtuin-5 (SIRT5) were analyzed by RT-qPCR and western blot assay. The proliferation levels of NHEKs were assessed by EdU staining. The expression of ELOVL1 and ELOVL4 was analyzed by RT-Qpcr, and the expression levels of filaggrin, loricrin, and aquaporin-3 were analyzed by RT-qPCR and western blot. Extracellular signal-regulated kinase 1/2 (ERK1/2) activator t-butylhydroquinone was used to activate ERK1/2. Here, we show that SIRT5 overexpression reduces cell viability and cell proliferation, and improves barrier dysfunction in IL-17A-treated human epidermal keratinocytes, this effect of which is significantly blunted by the ERK1/2 activator. In epidermal keratinocytes, SIRT5 decreases cell proliferation and inflammation and improves barrier dysfunction via ERK/STAT3. This study reveals the role of SIRT5 in the pathogenesis of psoriasis, epidermal hyperplasia, keratinocyte-mediated inflammatory responses, and barrier dysfunction, the role of which is mediated by ERK/STAT3.

Keywords: Dysfunction; ERK/STAT3; Epidermal Barrier; Inflammation; Proliferation; Psoriasis; SIRT5.

MeSH terms

  • Cells, Cultured
  • Epidermis / metabolism
  • Epidermis / pathology
  • Humans
  • Inflammation / pathology
  • Interleukin-17* / pharmacology
  • Keratinocytes* / metabolism
  • Keratinocytes* / pathology
  • Psoriasis* / metabolism
  • Psoriasis* / pathology
  • Sirtuins* / genetics
  • Sirtuins* / metabolism

Substances

  • Interleukin-17
  • SIRT5 protein, human
  • Sirtuins