SHORT PALATE LUNG AND NASAL EPITHELIUM 1 AND AIRWAY DISEASE
Public Deposited- Last Modified
- March 20, 2019
- Creator
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Huang, Julianne
- Affiliation: College of Arts and Sciences, Department of Chemistry
- Abstract
- Airway disease such as asthma and infection is the cause substantial morbidity and mortality in the world today. Although modern medicine has developed many drugs for these conditions, these diseases remain highly prevalent and are often difficult to treat. Short palate, lung and nasal epithelium clone 1 (SPLUNC1) is an abundant multi-functional protein in the airway. It has been reported to have immune-modulatory, surfactant and anti-microbial functions, and it regulates the airway surface liquid (ASL) height through the epithelial sodium channel (ENaC). This study focuses on utilizing SPLUNC1’s protective properties in combatting airway disease. Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, yet its pathophysiology is still poorly understood. SPLUNC1 is dysregulated in allergic rhinitis and chronic rhinosinusitis with nasal polyps. However, SPLUNC1 regulation in asthmatics has not been investigated. Here, we show that in allergic asthmatic humans and house dust mite (HDM)-allergic mice, SPLUNC1 in the bronchoalveolar lavage (BAL) is reduced. We demonstrate that administration of SPLUNC1 to mice decreases their AHR and show that the molecular basis for this effect involves the coordination of the N-terminus with an electrostatic patch on the protein’s body. We propose that SPLUNC1 be further investigated for use in reducing AHR. Pseudomonas aeruginosa, a primary lung pathogen in nosocomial pneumonia and in lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD), causes considerable morbidity and mortality. SPLUNC1 has been shown to neutralize and combat P. aeruginosa in vivo and in vitro. Here, we sought to establish a model for evaluating delivery of exogenous SPLUNC1 in acute lung infection and provide evidence that preemptive administration of SPLUNC1 may decrease bacterial burden. Lastly, we suggest that the administration of SPLUNC1 which we propose for asthma and lung infection results in SPLUNC1 mediated SPLUNC1 release in the lungs, effectively increasing the local protein concentration. This effect may utilize SPLUNC1’s natural protective properties to combat airway disease. We conclude that SPLUNC1 should be investigated further for use in asthma and bacterial pneumonia.
- Date of publication
- December 2016
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Redinbo, Matthew R.
- Tilley, Stephen
- Slep, Kevin
- Tarran, Robert
- Brustad, Eric
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2016
- Language
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This work has no parents.
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