CPT1A‐IL‐10‐mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury

作者：Muyun Wang, Di Wu, Ximing Liao, Haiyang Hu, Jing Gao, Linlin Meng, Feilong Wang, Wujian Xu, Shaoyong Gao, Jing Hua, Yuanyuan Wang, Qiang Li, Kun Wang, Wei Gao · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1785 · 被引用次数：46 · 研究领域：Immune cells in cancer、Immune Response and Inflammation、Fatty Acid Research and Health

Abstract Background Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common acute respiratory failure due to diffuse pulmonary inflammation and oedema. Elaborate regulation of macrophage activation is essential for managing this inflammatory process and maintaining tissue homeostasis. In the past decades, metabolic reprogramming of macrophages has emerged as a predominant role in modulating their biology and function. Here, we observed reduced expression of carnitine palmitoyltransferase 1A (CPT1A), a key rate‐limiting enzyme of fatty acid oxidation (FAO), in macrophages of lipopolysaccharide (LPS)‐induced ALI mouse model. We assume that CPT1A and its regulated FAO is involved in the regulation of macrophage polarization, which could be positive regulated by interleukin‐10 (IL‐10). Methods After nasal inhalation rIL‐10 and/or LPS, wild type (WT), IL‐10 ‐/‐ , Cre ‐ CPT1A fl/fl and Cre + CPT1A fl/fl mice were sacrificed to harvest bronchoalveolar lavage fluid, blood serum and lungs to examine cell infiltration, cytokine production, lung injury severity and IHC. Bone marrow‐derived macrophages (BMDMs) were extracted from mice and stimulated by exogenous rIL‐10 and/or LPS. The qRT‐PCR, Seahorse XFe96 and FAO metabolite related kits were used to test the glycolysis and FAO level in BMDMs. Immunoblotting assay, confocal microscopy and fluorescence microplate were used to test macrophage polarization as well as mitochondrial structure and function damage. Resu...