Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma.
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.
Chen
Ya-Hong
YH
Respiratory Department, Peking University Third Hospital, Beijing 100083, China. chenyahong@vip.sina.com
Wu
Rui
R
Geng
Bin
B
Qi
Yong-Fen
YF
Wang
Pei-Pei
PP
Yao
Wan-Zhen
WZ
Tang
Chao-Shu
CS
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
D013440:Sulfides; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide