1,25-Dihydroxyvitamin D3 prevented allergic asthma in a rat model by suppressing the expression of inducible nitric oxide synthase.
The active form of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] regulates calcium homeostasis, immunity, and other physiological processes while its effect in T-helper lymphocyte type 2 models is not very clear. The prevention effect of 1,25(OH)2D3 for allergic asthma in a rat asthma model was investigated. Healthy Wistar rats were randomly divided into four groups: control group, asthma group, drug prevention group, and treatment group. Asthma was induced in rats by sensitization and challenges with ovalbumin (OVA). The drug prevention group and treatment group were given 1,25(OH)2D3 or vitamin D3 on different schedules. The effects of 1,25(OH)2D3 on the development of asthma were analyzed. The airway hyperresponsiveness, the inflammatory cell infiltration in bronchoalveolar lavage (BAL) fluid, and histological changes of lung cells were examined. Nitric oxide production and the expression and activity of induced nitric oxide synthase (iNOS) in the lungs were examined also. Our study showed that 1,25(OH)2D3 reduced the airway inflammatory response in BAL. The concentration of NO and the activity and expression of iNOS in the lungs were decreased in the 1,25(OH)2D3 prevention and treatment groups. The expression of iNOS mRNA and protein levels were dose-dependently attenuated in the presence of 10(-13)-10(-8) mol/L of 1,25(OH)2D3 in alveolar macrophage culture. These findings collectively indicated that 1,25(OH)2D3 lowered many symptoms of inflammatory responses and decreased the expression of iNOS in OVA-induced experimental asthma. 1,25(OH)2D3 could be used as a new therapeutic agent in the treatment of asthma.
Department of Respiratory Medicine, Shanghai First Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
Yan
Y
Zhou
Xin
X
Zhou
Xiaoqiu
X
Wang
D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D018893:Bronchoalveolar Lavage / Q000379:methods; D002117:Calcitriol / Q000008:administration & dosage*; D002452:Cell Count; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D010047:Ovalbumin / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; D002117:Calcitriol