title: Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice.
abstract: Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), an H2S donor, was administered to the mice either before ozone exposure (preventive effect) or after completion of 6 weeks of ozone exposure (therapeutic effect). The ozone-exposed mice developed emphysema, measured by micro-computed tomography and histology, airflow limitation, measured by the forced maneuver system, and increased lung inflammation with augmented IL-1β, IL-18, and matrix metalloproteinase-9 (MMP-9) gene expression. Ozone-induced changes were associated with increased Nod-like receptor pyrin domain containing 3 (NLRP3)-caspase-1 activation and p38 mitogen-activated protein kinase phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed lung inflammation and emphysematous changes in alveolar space. In contrast, NaHS prevented, but did not reverse, ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of lung inflammation and emphysema via regulation of the NLRP3-caspase-1, p38 mitogen-activated protein kinase, and Akt pathways.
authors.affiliation: 1 Department of Respiratory Medicine and.
authors.forename: Feng
authors.identifier: 0000-0002-0646-6560
authors.initials: F
authors.lastname: Li
authors.affiliation: 1 Department of Respiratory Medicine and.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 1 Department of Respiratory Medicine and.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 2 Department of Respiratory Medicine, Shanghai Third People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: 1 Department of Respiratory Medicine and.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: 3 Experimental Research Center, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: 3 Experimental Research Center, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 1 Department of Respiratory Medicine and.
authors.forename: Aihua
authors.initials: A
authors.lastname: Bao
authors.affiliation: 4 Division of Environmental Sciences and Policy, Nicholas School of the Environment and Duke Global Health Institute, Duke University, Durham, North Carolina; and.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Gong
authors.affiliation: 4 Division of Environmental Sciences and Policy, Nicholas School of the Environment and Duke Global Health Institute, Duke University, Durham, North Carolina; and.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 5 Airway Diseases Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.affiliation: 5 Airway Diseases Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: 1 Department of Respiratory Medicine and.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D020690:GTPase-Activating Proteins; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D021621:Imaging, Three-Dimensional; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000378:metabolism; D010126:Ozone / Q000009:adverse effects*; D010766:Phosphorylation; D011014:Pneumonia / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D055114:X-Ray Microtomography; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C576656:Nprl3 protein, mouse; D016877:Oxidants; D012333:RNA, Messenger; D010126:Ozone; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D020170:Caspase 1; D006862:Hydrogen Sulfide
keywords: emphysema; hydrogen sulfide; lung inflammation; ozone exposure