IL-38 alleviates atherogenic responses via SIRT6/HO-1 signaling: A promising strategy against obesity-related atherosclerosis

Cho W., Oh H., HASSIBELNABY A. M. A., Mobarak E. H., Jeong J. H., Jung T. W.

Biochemical and Biophysical Research Communications, vol.694, 2024 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 694
  • Publication Date: 2024
  • Doi Number: 10.1016/j.bbrc.2023.149407
  • Journal Name: Biochemical and Biophysical Research Communications
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, Veterinary Science Database
  • Keywords: Atherosclerosis, IL-38, HUVEC, THP-1, SIRT6, HO-1
  • Ataturk University Affiliated: Yes

Abstract

Interleukin-38 (IL-38), a member of the IL-1 family, is known for its anti-inflammatory properties mediated through ligand signaling in various disease models. It plays a significant role in atherosclerosis development, forming a theoretical basis for therapeutic strategies. However, the direct effects of IL-38 on atherogenic responses in the vascular endothelium and monocytes remain unclear. In this investigation, IL-38 treatment reduced THP-1 monocyte adhesion to HUVECs, decreased the expression of vascular adhesion molecules, and mitigated inflammation in the presence of palmitate. IL-38 treatment upregulated SIRT6 expression and enhanced autophagy markers such as LC3 conversion and p62 degradation. The effects of IL-38 were nullified by siRNA-mediated suppression of SIRT6 or heme oxygenase-1 (HO-1) in HUVECs and palmitate-treated THP-1 cells. These findings reveal that IL-38 mitigates inflammation through the SIRT6/HO-1 pathway, offering a potential therapeutic approach for addressing obesity-related atherosclerosis.