Assessing the Effects of Nicotinamide Mononucleotide Supplementation on Pulmonary Inflammation in Male Mice Subchronically Exposed to Ambient Particulate Matter

被引：9

作者：

Zhang, Rui ^{[1
]}

Chen, Shen ^{[1
]}

Wang, Ziwei ^{[1
]}

Ye, Lizhu ^{[1
]}

Jiang, Yue ^{[1
]}

Li, Miao ^{[1
]}

Jiang, Xinhang ^{[1
]}

Peng, Hui ^{[1
]}

Guo, Zhanyu ^{[1
]}

Chen, Liping ^{[1
]}

Zhang, Rong ^{[2
]}

Niu, Yujie ^{[2
]}

Aschner, Michael ^{[3
]}

Li, Daochuan ^{[1
]}

Chen, Wen ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Publ Hlth, Dept Toxicol, Guangzhou, Peoples R China

[2] Hebei Med Univ, Sch Publ Hlth, Dept Toxicol, Shijiazhuang, Peoples R China

[3] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY USA

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 2023年 / 131卷 / 07期

基金：

中国国家自然科学基金;

关键词：

ANALYSIS PROGRAM; PM2.5; EXPOSURE; HEALTH; FIBROSIS; LUNG; CHOLESTEROL; DECLINE; IMPACT;

D O I：

10.1289/EHP12259

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

BACKGROUND: Chronic lung injury and dysregulated cellular homeostasis in response to particulate matter (PM) exposure are closely associated with adverse health effects. However, an effective intervention for preventing the adverse health effects has not been developed.OBJECTIVES: This study aimed to evaluate the protective effects of nicotinamide mononucleotide (NMN) supplementation on lung injury and elucidate the mechanism by which NMN improved immune function following subchronic PM exposure. METHODS: Six-week-old male C57BL/6J mice were placed in a real-ambient PM exposure system or filtered air-equipped chambers (control) for 16 wk with or without NMN supplementation in drinking water (regarded as Con-H2O, Exp-H2O, Con-NMN and Exp-NMN groups, respectively) in Shijiazhuang City, China (n = 20/group). The effects of NMN supplementation (500 mg/kg) on PM-induced chronic pulmonary inflammation were assessed, and its mechanism was characterized using single-cell transcriptomic sequencing (scRNA-seq) analysis of whole lung cells.RESULTS: The NMN-treated mice exhibited higher NAD+ levels in multiple tissues. Following 16-wk PM exposure, slightly less pulmonary inflammation and less collagen deposition were noted in mice with NMN supplementation in response to real-ambient PM exposure (Exp-NMN group) compared with the Exp-H2O group (all p < 0.05). Mouse lung tissue isolated from the Exp-NMN group was characterized by fewer neutrophils, monocyte-derived cells, fibroblasts, and myeloid-derived suppressor cells induced by subchronic PM exposure as detected by scRNA-seq transcriptomic analysis. The improved immune functions were further characterized by interleukin-17 signaling pathway inhibition and lower secretion of pro fibrotic cytokines in the Exp-NMN group compared with the Exp-H2O group. In addition, reduced proportions of differentiated myofibroblasts and profibrotic interstitial macrophages were identified in the NMN-supplemented mice in response to PM exposure. Furthermore, less immune function suppression and altered differentiation of pathological cell phenotypes NMN was related to intracellular lipid metabolism activation.DISCUSSION: Our novel findings suggest that NMN supplementation mitigated PM-induced lung injury by regulating immune functions and improving lipid metabolism in male mice, providing a putative intervention method for prevention of human health effects associated with PM exposure. https:// doi.org/10.1289/EHP12259

引用

页数：18

共 21 条

[21] Combined adjuvant effects of ambient vapor-phase organic components and particulate matter potently promote allergic sensitization and Th2-skewing cytokine and chemokine milieux in mice: The importance of mechanistic multi-pollutant research
Li, Ning
Lewandowski, Ryan P.
Sidhu, Damansher
Holz, Carine
Jackson-Humbles, Daven
Eiguren-Fernandez, Arantzazu
Akbari, Peyman
Cho, Arthur K.
Harkema, Jack R.
Froines, John R.
Wagner, James G.
TOXICOLOGY LETTERS, 2022, 356 : 21 - 32

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