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

Abstract

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 (IκBα) expression was determined by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated IκBα 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 IκBα protein levels via inducing increased IκBα mRNA levels and decreased IκBα phosphorylation. Conclusion. 1,25-(OH)₂D₃ could attenuate asthmatic airway remodeling and its inhibition of NF-κB activation may underlie this protective effect.

• airway remodeling
• asthma
• 1,25-dihydroxyvitamin D₃
• IκBα
• nuclear factor kappa B

Acknowledgments

We thank Dr. Deling Liu for a critical reading of the manuscript and for helpful discussions and Dr. Qingan Lin for excellent technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the contents and writing of this article.

This study was supported by the National Natural Science Foundation of China (Grant No. 81100011).