This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ikeda, R. K. Articles by Broide, D. H. Search for Related Content PubMed PubMed Citation Articles by Ikeda, R. K. Articles by Broide, D. H.

Resolution of Airway Inflammation following Ovalbumin Inhalation

Comparison of ISS DNA and Corticosteroids

Department of Medicine, University of California-San Diego, La Jolla, California

Address correspondence to: Dr. David H. Broide, M.B.Ch.B., University of California-San Diego, Basic Science Building, Room 5090, 9500 Gilman Drive, La Jolla, CA 92093-0635. E-mail: dbroide{at}ucsd.edu

In this study we have compared the therapeutic effect of the administration of immunostimulatory DNA sequences (ISS) with that of corticosteroids on the resolution of airway inflammation and airway hyperreactivity (AHR) in a mouse model. Mice which had already developed significant levels of eosinophilic airway inflammation 24 h after allergen challenge were then treated with either ISS or corticosteroids, and the effect on AHR and airway inflammation assessed 6 d later. ISS inhibited AHR as effectively as corticosteroids. Combination therapy with ISS and corticosteroids was more effective than monotherapy with either ISS or corticosteroids in inhibiting AHR. In ovalbumin-challenged mice, levels of bronchoalveolar lavage (BAL) eosinophils were significantly reduced with either ISS or corticosteroids. ISS induced significant levels of BAL interferon-, whereas corticosteroids did not induce expression of BAL interferon-. Both ISS and corticosteroids significantly reduced levels of interleukin-5 in BAL, as well as the number of Periodic Acid Schiff–positive airway epithelial cells. Corticosteroids, but not ISS, increased the number of eosinophils in regional mediastinal lymph nodes. Very few apoptotic peribronchial cells were noted following ovalbumin challenge as assessed by TUNEL assay. Corticosteroids, but not ISS, induced an increase in the small number of apoptotic peribronchial cells. The mechanism by which either ISS or corticosteroids inhibit AHR is likely to be mediated by distinct and shared cellular pathways. The combination of the shared and distinct anti-inflammatory pathways may account for the additive effect of ISS and corticosteroids on inhibiting AHR.

Abbreviations: airway hyperresponsiveness, AHR • bronchoalveolar lavage, BAL • BAL fluid, BALF • dynamic compliance, Cdyn • diaminobenzidine, DAB • interferon, IFN • interleukin, IL • immunostimulatory DNA sequence, ISS • methacholine, MCh • ovalbumin, OVA • Periodic Acid Schiff, PAS • Toll-like receptor 9, TLR-9

This article has been cited by other articles:

				C. J. Le Saux, K. Teeters, S. K. Miyasato, P. R. Hoffmann, O. Bollt, V. Douet, R. V. Shohet, D. H. Broide, and E. K. Tam Down-regulation of Caveolin-1, an Inhibitor of Transforming Growth Factor-{beta} Signaling, in Acute Allergen-induced Airway Remodeling J. Biol. Chem., February 29, 2008; 283(9): 5760 - 5768. [Abstract] [Full Text] [PDF]

				S. R. Kim, K. S. Lee, S. J. Park, K. H. Min, K. Y. Lee, Y. H. Choe, Y. R. Lee, J. S. Kim, S. J. Hong, and Y. C. Lee PTEN Down-Regulates IL-17 Expression in a Murine Model of Toluene Diisocyanate-Induced Airway Disease J. Immunol., November 15, 2007; 179(10): 6820 - 6829. [Abstract] [Full Text] [PDF]

				E. H. Walters, D. W. Reid, D. P. Johns, and C. Ward Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling Eur. Respir. J., September 1, 2007; 30(3): 574 - 588. [Abstract] [Full Text] [PDF]

				K. S. Lee, S. J. Park, S. R. Kim, K. H. Min, S. M. Jin, H. K. Lee, and Y. C. Lee Modulation of Airway Remodeling and Airway Inflammation by Peroxisome Proliferator-Activated Receptor {gamma} in a Murine Model of Toluene Diisocyanate-Induced Asthma J. Immunol., October 15, 2006; 177(8): 5248 - 5257. [Abstract] [Full Text] [PDF]

				W. R. Henderson Jr., G. K. S. Chiang, Y.-t. Tien, and E. Y. Chi Reversal of Allergen-induced Airway Remodeling by CysLT1 Receptor Blockade Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 718 - 728. [Abstract] [Full Text] [PDF]

				M. V. Fanucchi, E. S. Schelegle, G. L. Baker, M. J. Evans, R. J. McDonald, L. J. Gershwin, E. Raz, D. M. Hyde, C. G. Plopper, and L. A. Miller Immunostimulatory Oligonucleotides Attenuate Airways Remodeling in Allergic Monkeys Am. J. Respir. Crit. Care Med., December 1, 2004; 170(11): 1153 - 1157. [Abstract] [Full Text] [PDF]

				J. Y. Cho, M. Miller, K. J. Baek, J. W. Han, J. Nayar, M. Rodriguez, S. Y. Lee, K. McElwain, S. McElwain, E. Raz, et al. Immunostimulatory DNA Inhibits Transforming Growth Factor-{beta} Expression and Airway Remodeling Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 651 - 661. [Abstract] [Full Text] [PDF]

				S. T Holgate The epidemic of asthma and allergy J R Soc Med, March 1, 2004; 97(3): 103 - 110. [Full Text] [PDF]

				R. K. Ikeda, M. Miller, J. Nayar, L. Walker, J. Y. Cho, K. McElwain, S. McElwain, E. Raz, and D. H. Broide Accumulation of Peribronchial Mast Cells in a Mouse Model of Ovalbumin Allergen Induced Chronic Airway Inflammation: Modulation by Immunostimulatory DNA Sequences J. Immunol., November 1, 2003; 171(9): 4860 - 4867. [Abstract] [Full Text] [PDF]

				E. S. Silverman and J. M. Drazen Immunostimulatory DNA for Asthma: Better than Eating Dirt Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 645 - 647. [Full Text] [PDF]