Investigation into the Bronchoprotective and Anti-inflammatory Properties of RGS2

The clinical management of asthma involves treatment with inhaled corticosteroids (ICS) and long-acting β2-adrenoceptor agonists (LABAs). Regulator of G-protein signalling (RGS) 2 inhibits signalling from Gq protein-coupled receptors. In humans, combinations of a glucocorticoid and a LABA synergistically enhanced the expression of RGS2. In mice, 3 weeks of HDM challenge or 30 min of LPS challenge reduced lung function and induced airways inflammation. Compared to wild-type, Rgs2-/- mice showed significantly increased airways resistance and reduced compliance, in both HDM- and LPS-challenges. There was no difference between wild-type and Rgs2-/- mice in HDM-induced and LPS-induced inflammation. There was a trend towards increased inflammatory cell counts in the BALF of Rgs2-/- compared to wild-type. There was a trend towards increased expression for many HDM-induced cytokines/chemokines in Rgs2-/-. There was no difference between wild-type and Rgs2-/- mice in LPS-induced expression of cytokines/chemokines. These data show Rgs2 is bronchoprotective in HDM-induced inflammation and suggest a modest anti-inflammatory role. Rgs2 is bronchoprotective in LPS-induced inflammation, but more studies are required to address a possible anti-inflammatory role. If applicable to humans, these data suggest that therapeutics, for example ICS/LABA combination therapies, which are designed to maximize RGS2 expression, will be beneficial for asthma control and management.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Cardiovascular & Respiratory Sciences

Grantor dc:publisher.institution

Cumming School of Medicine

Year dc:date.issued

2016

Author dc:creator

• George, Tresa

Advisor dc:contributor.advisor

• Newton, Robert

Committee members dc:contributor.committeemember

• Giembycz, Mark
• Kelly, Margaret

• Genetics
• Biology--Molecular
• Pharmacology
• Biochemistry

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/26649

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/3283