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

• Chunhui Wang ^[1] ; Danhua He ^[2] ; Cuiping Shi ^[3]
  1. [1] Southern Medical University

     Southern Medical University

     China

     
  2. [2] Department of Dermatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, Guangdong, China.
  3. [3] Department of Dermatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.

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• Localización: Allergologia et immunopathologia: International journal for clinical and investigate allergology and clinical immunology, ISSN-e 1578-1267, ISSN 0301-0546, Vol. 51, Nº. 1, 2023, págs. 30-36
• Idioma: inglés
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• Resumen

  • 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.