IngentaConnect 1,25-Dihydroxyvitamin D3 prevented allergic asthma in a rat model...

Abstract:

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.

Keywords: Alveolar macrophages; asthma; dexamethasone; 1,25-dihydroxyvitamin D3; induced nitric oxide synthase; nitric oxide; vitamin D3

Document Type: Research article

DOI: 10.2500/aap.2008.29.3115

Affiliations: 1: Department of Respiratory Medicine, Shanghai First Hospital, Shanghai Jiao Tong University, Shanghai 200080, China

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1,25-Dihydroxyvitamin D3 prevented allergic asthma in a rat model by suppressing the expression of inducible nitric oxide synthase

1,25-Dihydroxyvitamin D₃ prevented allergic asthma in a rat model by suppressing the expression of inducible nitric oxide synthase