Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis

• Published in: Ecotoxicology and environmental safety 2022-12, Vol.247, p.114253-114253, Article 114253
• Main Authors: Peng, Renzhen, Yang, Wenhui, Shao, Wenpu, Pan, Bin, Zhu, Yaning, Zhang, Yubin, Kan, Haidong, Xu, Yanyi, Ying, Zhekang
• Format: Article
• Language: English
• Subjects: Glucose homeostasis; IL-6R; Inflammation; PM2.5; Pulmonary dysfunction
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.114253

Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1β and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure. [Display omitted] •IL-6R deficiency alleviates PM2.5 exposure-induced pulmonary dysfunction.•IL-6R deficiency aggravates PM2.5-induced glucose intolerance and insulin resistance.•PM2.5 induces adipose hypertrophy and inflammation in WT and IL-6R deficient mice.•IL-6R deficiency reduces PM2.5-induced pulmonary but not extra-pulmonary inflammation.