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Vol. 142, No. 3, 2007
Issue release date: February 2007
Section title: Original Paper
Int Arch Allergy Immunol 2007;142:219–229
(DOI:10.1159/000097024)

Dexamethasone Alters Bronchoalveolar Lavage Fluid Proteome in a Mouse Asthma Model

Zhao J. · Yeong L.H. · Wong W.S.F.
Department of Pharmacology, Yong Loo Lin School of Medicine, and Immunology Program, National University of Singapore, Singapore

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/20/2006
Accepted: 7/25/2006
Published online: 11/14/2006

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 2

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

Abstract

Background: Glucocorticoid is the most effective anti-inflammatory agent for asthma. The spectrum of protein targets that can be regulated by glucocorticoid in asthma is not fully understood. The present study tried to identify novel protein targets of dexamethasone in allergic airway inflammation by analyzing the proteome of mouse bronchoalveolar lavage (BAL) fluid. Methods: BALB/c mice sensitized and challenged with ovalbumin (OVA) showed increased pulmonary inflammatory cell infiltration, airway mucus production and serum OVA-specific IgE level. Dexamethasone inhibited all these allergic airway inflammation endpoints. BAL fluid proteins were resolved by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: The levels of 26 BAL fluid proteins were found to be markedly altered by dexamethasone. A family of chitinases (Ym1, Ym2 and acidic mammalian chitinase, AMCase), lungkine, gob-5, surfactant protein D and polymeric immunoglobulin receptor have been found for the first time to be downregulated by dexamethasone in allergic airways. The downregulatory effects were confirmed by immunoblotting and RT-PCR analyses. Dexamethasone was also shown to significantly inhibit lavage fluid chitinase bioactivity. In addition, dexamethasone promoted airway expression of vitamin D-binding protein, heptoglobin and α1-antitrypsin. Conclusions: Among all these newly identified protein targets of dexamethasone, AMCase and gob-5 have been shown to be pro-inflammatory in asthma. Downregulation of AMCase and gob-5 may be considered as two novel anti-inflammatory actions of glucocorticoid in asthma.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/20/2006
Accepted: 7/25/2006
Published online: 11/14/2006

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 2

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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