Chronic rhinosinusitis (CRS) is a very common upper airway disease affecting more than 31 million Americans. Current therapeutic strategies for CRS include both medical and surgical treatments;one major goal of these treatments is to improve the nasal mucociliary clearance (MCC) function in CRS patients, as this may reverse the diseased sinonasal mucosa to achieve physiological recovery. Adenosine is a ubiquitous nucleoside normally present in the airway lumen and interstitium. Previous in vitro studies have shown that adenosine is the major regulator for nasal airway surface liquid homeostasis. It can also increase cilia beating frequency of cultured human nasal epithelium. In our preliminary in vivo studies, a potent effect of adenosine, but not ATP, to accelerate nasal MCC was also observed. These findings indicate that adenosine and its receptors may be of great therapeutic value for CRS by speeding up nasal MCC. In addition to regulating MCC, adenosine has also been shown to elicit both anti- and pro-inflammatory effects. Although previous studies in the lower airways have revealed that adenosine enhances inflammation, our preliminary studies have shown that adenosine is not pro-inflammatory in the nose and sinuses. Based on all of these findings, we hypothesize that adenosine is the key factor to enhance the nasal MCC in vivo (Aim 1) and its anti-inflammatory actions will attenuate the development of CRS (Aim 2). The effect of adenosine on nasal MCC will be tested in vivo at both healthy and inflamed nose and sinuses. The underlying mechanisms will be determined at both in vivo and in vitro levels. The role of adenosine and adenosine receptors in CRS development, progression, and resolution will also be examined. We believe that the completion of this translational project will lead to a novel therapeutic strategy for CRS. It will also be of great significance to enhancing our knowledge of adenosine airway biology and re-evaluating the unified airway theory.

Public Health Relevance

Chronic rhinosinusitis (CRS) is a very common inflammatory disease in the nose and sinuses. Currently, both medical and surgical therapies are used for CRS patients;however, many patients still present with persistent inflammation even after aggressive treatment. In the proposed studies, we will examine the role of adenosine, a common mediator in human body, and its receptors, in CRS development, and explore the therapeutic value of targeting adenosine receptors for the treatment of CRS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI096139-01A1
Application #
8243944
Study Section
Lung Cellular, Molecular, and Immunobiology Study Section (LCMI)
Program Officer
Togias, Alkis
Project Start
2012-02-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$185,000
Indirect Cost
$60,000
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Hua, Xiaoyang; Naselsky, Warren C; Bennett, William D et al. (2013) Adenosine increases nasal mucociliary clearance rate in mice through A2A and A2B adenosine receptors. Laryngoscope 123:306-10
Hua, Xiaoyang; Chason, Kelly D; Jania, Corey et al. (2013) Gs-coupled adenosine receptors differentially limit antigen-induced mast cell activation. J Pharmacol Exp Ther 344:426-35