Interleukin-38 Ameliorates Atherosclerosis by Inhibiting Macrophage M1-like Polarization and Apoptosis

作者：Zhiyang Li, Xue‐Lian Li, Rui Shen, Yue Wang, Jian Yu, Chengliang Pan, Yifan Cai, Qian Dong, Kunwu Yu, Qiutang Zeng · 发表于：Biomolecules · 年份：2025 · DOI：10.3390/biom15121741 · 被引用次数：3 · 研究领域：Immune cells in cancer、Psoriasis: Treatment and Pathogenesis、Adipokines, Inflammation, and Metabolic Diseases

OBJECTIVES: As a novel member of the interleukin(IL)-1 family, IL-38 has shown therapeutic effects in various chronic inflammatory diseases. However, its role and underlying mechanisms in cardiovascular diseases, particularly atherosclerosis, remain unclear. This study aimed to explore the effects of IL-38 on atherosclerosis progression and its mechanisms in regulating macrophage function during the atherosclerotic process. METHODS: To evaluate the therapeutic potential of IL-38 in atherosclerosis, we performed histopathological examinations and biochemical analyses in vivo. In vitro, we used primary bone marrow-derived macrophages (BMDMs) stimulated with oxidized low-density lipoprotein (ox-LDL) to assess the anti-inflammatory effects of IL-38 and quantified its impact on ox-LDL-induced macrophage polarization. To further elucidate the specific mechanisms by which IL-38 regulates macrophage function, we conducted mRNA sequencing and validated downstream regulatory signaling pathways. RESULTS: IL-38 exhibited therapeutic potential in atherosclerosis by reducing atherosclerotic plaque formation, modulating plaque composition, suppressing the production of proinflammatory cytokines within plaques, and potentially regulating macrophage cholesterol metabolism. Moreover, IL-38 exerted significant anti-inflammatory effects on macrophages both in vivo and in vitro. Notably, it inhibited the polarization of macrophages toward the proinflammatory M1-like phenotype in both settings. Ad...