TY - JOUR
T1 - Assessing the Effects of Nicotinamide Mononucleotide Supplementation on Pulmonary Inflammation in Male Mice Subchronically Exposed to Ambient Particulate Matter
AU - Zhang, Rui
AU - Chen, Shen
AU - Wang, Ziwei
AU - Ye, Lizhu
AU - Jiang, Yue
AU - Li, Miao
AU - Jiang, Xinhang
AU - Peng, Hui
AU - Guo, Zhanyu
AU - Chen, Liping
AU - Zhang, Rong
AU - Niu, Yujie
AU - Aschner, Michael
AU - Li, Daochuan
AU - Chen, Wen
N1 - Publisher Copyright:
© 2023, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2023/7
Y1 - 2023/7
N2 - 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 eluci-date 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 transcrip-tomic 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.
AB - 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 eluci-date 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 transcrip-tomic 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.
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U2 - 10.1289/EHP12259
DO - 10.1289/EHP12259
M3 - Article
C2 - 37458712
AN - SCOPUS:85165039169
SN - 0091-6765
VL - 131
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 7
M1 - 077006
ER -