1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) Attenuates Airway Remodeling in a Murine Model of Chronic Asthma.

Objectives. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has immune- and inflammation-modulating properties in asthma, but its possible effects on asthmatic airway remodeling remain uncertain. In this study, we investigated the effects of 1,25-(OH)2D3 on airway remodeling in a murine model of chronic asthma and investigated its role in regulating nuclear factor- κB (NF- κB) activation. Methods. BALB/c mice were sensitized to ovalbumin (OVA) and subsequently exposed to intranasal OVA challenges for 9 weeks. Some mice also received an intraperitoneal injection of 1,25-(OH)2D3 at the time of challenge. At the end of the challenge period, mice were evaluated for chronic airway inflammation and airway remodeling. Nuclear translocation of NF- κB p65 in lung tissue was examined by Western blot. Inhibitor of NF- κB alpha (I κB α) expression was determined by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated I κB α protein expression was also determined by Western blot. Results. 1,25-(OH)2D3 treatment reduced OVA-induced chronic inflammation in lung tissue and attenuated established structural changes of the airways, including subepithelial collagen deposition, goblet cell hyperplasia, and increased airway smooth muscle mass. 1,25-(OH)2D3 also inhibited the nuclear translocation of NF- κB p65 in lung tissue. Concurrently, 1,25-(OH)2D3 induced increased I κB α protein levels via inducing increased I κB α mRNA levels and decreased I κBα phosphorylation. Conclusion. 1,25-(OH)2D3 could attenuate asthmatic airway remodeling and its inhibition of NF- κB activation may underlie this protective effect. [ABSTRACT FROM AUTHOR]