VBP15, a Glucocorticoid Analogue, Is Effective at Reducing Allergic Lung Inflammation in Mice

Damsker, Jesse M., Dillingham, Blythe C., Rose, Mary C., Balsley, Molly A., Heier, Christopher R., Watson, Alan M., Stemmy, Erik J., Jurjus, Roslyn A., Huynh, Tony, Tatem, Kathleen, Uaesoontrachoon, Kitipong, Berry, Dana M., Benton, Angela S., Freishtat, Robert J., Hoffman, Eric P., McCall, John M., Gordish-Dressman, Heather, Constant, Stephanie L., Reeves, Erica K. M. and Nagaraju, Kanneboyina (2013) VBP15, a Glucocorticoid Analogue, Is Effective at Reducing Allergic Lung Inflammation in Mice. PLoS One, 8 5: e63871.1-e63871.9. doi:10.1371/journal.pone.0063871

Author Damsker, Jesse M.
Dillingham, Blythe C.
Rose, Mary C.
Balsley, Molly A.
Heier, Christopher R.
Watson, Alan M.
Stemmy, Erik J.
Jurjus, Roslyn A.
Huynh, Tony
Tatem, Kathleen
Uaesoontrachoon, Kitipong
Berry, Dana M.
Benton, Angela S.
Freishtat, Robert J.
Hoffman, Eric P.
McCall, John M.
Gordish-Dressman, Heather
Constant, Stephanie L.
Reeves, Erica K. M.
Nagaraju, Kanneboyina
Title VBP15, a Glucocorticoid Analogue, Is Effective at Reducing Allergic Lung Inflammation in Mice
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-05-07
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0063871
Open Access Status DOI
Volume 8
Issue 5
Start page e63871.1
End page e63871.9
Total pages 9
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2013
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
Abstract Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel series of steroidal analogues (VBP compounds) that have been previously shown to maintain anti-inflammatory properties such as NFκB-inhibition without inducing glucocorticoid receptor-mediated gene transcription. This study was undertaken to determine the effectiveness of the lead compound, VBP15, in a mouse model of allergic lung inflammation. We show that VBP15 is as effective as the traditional glucocorticoid, prednisolone, at reducing three major hallmarks of lung inflammation-NFκB activity, leukocyte degranulation, and pro-inflammatory cytokine release from human bronchial epithelial cells obtained from patients with asthma. Moreover, we found that VBP15 is capable of reducing inflammation of the lung in vivo to an extent similar to that of prednisone. We found that prednisolone-but not VBP15 shortens the tibia in mice upon a 5 week treatment regimen suggesting effective dissociation of side effects from efficacy. These findings suggest that VBP15 may represent a potent and safer alternative to traditional glucocorticoids in the treatment of asthma and other inflammatory diseases.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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