title: Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma.
abstract: Endogenous hydrogen sulfide (H(2)S) is hypothesized to have an important role in systemic inflammation. We investigated if endogenous H(2)S may be a crucial mediator in airway inflammation and airway remodeling in a rat model of asthma and if endogenous H(2)S may exert its anti-inflammatory effect by inhibiting inducible nitric oxide synthase (iNOS)/NO pathway. Cystathionine-gamma-lyase (CSE; a H(2)S-synthesizing enzyme) was mainly expressed in airway and vascular smooth muscle cells in rat lung tissue. Levels of endogenous H(2)S was decreased in pulmonary tissue in ovalbumin (OVA)-treated rats. Exogenous administration of NaHS alleviated airway inflammation and airway remodeling: peak expiratory flow (PEF) increased, goblet cell hyperplasia and collagen deposition score decreased, with decreased total cells recovered from bronchoalveolar fluid (BALF) and influx of eosinophils and neutrophils. The H(2)S levels of serum and lung tissue were positively correlated with PEF and negatively correlated with the level of eosinophils and neutrophils in BALF, score of lung pathology. NaHS treatment significantly attenuated pulmonary iNOS activation in OVA-treated rats. These results suggest that the CSE/H(2)S pathway plays an anti-inflammatory and anti-remodeling part in asthma pathogenesis and could be a novel target in prevention and treatment of asthma.
authors.affiliation: Respiratory Department, Peking University Third Hospital, Beijing 100083, China. chenyahong@vip.sina.com
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Wang
authors.forename: Wan-Zhen
authors.initials: WZ
authors.lastname: Yao
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D013440:Sulfides; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide