IL-38 alleviates atherogenic responses<i> via</i> SIRT6/HO-1 signaling: A promising strategy against obesity-related atherosclerosis
Cho, Wonjun, Oh, Heeseung, Abd El-Aty, A. M., Mobarak, Enas H., Jeong, Ji Hoon, Jung, Tae Woo
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 re-sponses 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.
- Journal
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Year
- 2024
- Volume
- 694
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- DOI
- 10.1016/j.bbrc.2023.149407
- WoS UID
- WOS:001165704300001