The impact of vitamin D on asthmatic human airway smooth muscle

ABSTRACT

Asthma is a chronic heterogeneous disorder, which involves airway inflammation, airway hyperresponsiveness (AHR) and airway remodeling. The airway smooth muscle (ASM) bundle regulates the broncho-motor tone and plays a critical role in AHR as well as orchestrating inflammation. Vitamin D deficiency has been linked to increased severity and exacerbations of symptoms in asthmatic patients. It has been shown to modulate both immune and structural cells, including ASM cells, in inflammatory diseases. Given that current asthma therapies have not been successful in reversing airway remodeling, vitamin D supplementation as a potential therapeutic option has gained a great deal of attention. Here, we highlight the potential immunomodulatory properties of vitamin D in regulating ASM function and airway inflammation in bronchial asthma.

KEYWORDS:

• Asthma airway hyperresponsiveness airway smooth muscle cells
• immunomodulation remodeling vitamin D

Financial & competing interests disclosure

This work was supported by research grants R01 HL116042, R01 HL112597, and R01 HL120659 to DK Agrawal from the Office of the Director, National Institutes of Health, and National Heart, Lung and Blood Institute, NIH USA. The content of this review is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

ORCID

Devendra K. Agrawala http://orcid.org/0000-0001-5445-0013

Key issues

• Airway smooth muscle (ASM) bundles regulate the broncho-motor tone and are the main effectors of bronchial contraction in human airways. They are also able to orchestrate inflammation leading to airway hyperresponsiveness and remodeling.

• The ASM bundle is aberrant in asthmatic patients and current therapeutic options are not effective at altering airway remodeling.

• Vitamin D deficiency has been associated with increased airway inflammation and exacerbations in asthmatic patients.

• ASM cells express a functionally active vitamin D receptor.

• Vitamin D has been shown to decrease ASM proliferation, migration as well as cytokine secretion in vitro.

• Though there is a clear link between vitamin D status and airway inflammation in asthma, results from clinical trials are inconclusive.

• Targeted clinical trials are needed to conclusively decipher whether or not vitamin D supplementation is a viable treatment option for asthmatics.