糖原代谢重编程促进煤尘暴露肺的炎症。

Glycogen metabolism reprogramming promotes inflammation in coal dust-exposed lung.

机构信息

Key Laboratory of Industrial Dust Control and Occupational Health of the Ministry of Education, Anhui University of Science and Technology, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, China; School of Medicine, Department of Medical Frontier Experimental Center, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, China.

出版信息

Ecotoxicol Environ Saf. 2022 Sep 1;242:113913. doi: 10.1016/j.ecoenv.2022.113913. Epub 2022 Jul 27.

DOI:10.1016/j.ecoenv.2022.113913

PMID:35907323

Abstract

Long-term coal dust exposure triggers complex inflammatory processes in the coal workers' pneumoconiosis (CWP) lungs. The progress of the inflammation is reported to be affected by disordered cell metabolism. However, the changes in the metabolic reprogramming associated with the pulmonary inflammation induced by the coal dust particles are unknown. Herein, we show that coal dust exposure causes glycogen accumulation and the reprogramming of glucose metabolism in the CWP lung. The glycogen accumulation caused by coal dust is mainly due to macrophages, which reprogram glycogen metabolism and trigger an inflammatory response. In addition, 2-deoxy-D-glucose (2-DG) reduced glycogen content in macrophages, which was accompanied by mitigated inflammation and restrained NF-κB activation. Accordingly, we have pinpointed a novel and crucial metabolic pathway that is an essential regulator of the inflammatory phenotype of coal dust-exposed macrophages. These results shed light on new ways to regulate CWP inflammation.

摘要

长期的煤尘暴露会引发煤工尘肺（CWP）肺部的复杂炎症过程。据报道，炎症的进展受到细胞代谢紊乱的影响。然而，煤尘颗粒引起的肺部炎症相关的代谢重编程变化尚不清楚。在此，我们发现煤尘暴露会导致 CWP 肺中糖原积累和葡萄糖代谢的重新编程。煤尘引起的糖原积累主要是由于巨噬细胞，巨噬细胞重新编程糖原代谢并引发炎症反应。此外，2-脱氧-D-葡萄糖（2-DG）降低了巨噬细胞中的糖原含量，伴随炎症减轻和 NF-κB 激活受到抑制。因此，我们确定了一条新的、关键的代谢途径，该途径是调控暴露于煤尘的巨噬细胞炎症表型的重要调节剂。这些结果为调控 CWP 炎症提供了新的思路。