HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

Cyclooxygenase Inhibition Augments Allergic Inflammation through CD4-Dependent, STAT6-Independent Mechanisms¹

Koichi Hashimoto^2,*, James R. Sheller^*, Jason D. Morrow^*, Robert D. Collins, Kasia Goleniewska^*, Jamye O’Neal^*, Weisong Zhou^*, Shaoquan Ji, Daphne B. Mitchell^*, Barney S. Graham and R. Stokes Peebles, Jr^3,*

Departments of ^* Medicine and Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232; LINCO Research, St. Charles, MO 63304; and Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892

Nonselective cyclooxygenase (COX) inhibition during the development of allergic disease in a murine model causes an increase in type 2 cytokines and lung eosinophilia; however, the mechanisms responsible for this augmented allergen-induced inflammation have not been examined. Ab depletion of CD4 and CD8 cells revealed that the heightened allergic inflammation caused by COX inhibition was CD4, but not CD8, dependent. Allergen sensitization and airway challenge alone led to undetectable levels of IL-5 and IL-13 in the lungs of IL-4, IL-4R, and STAT6 knockout (KO) mice, but COX inhibition during the development of allergic inflammation resulted in wild-type levels of IL-5 and IL-13 and heightened airway eosinophilia in each of the three KO mice. These results indicate that the effect of COX inhibition was independent of signaling through IL-4, IL-4R, and STAT6. However, whereas COX inhibition increased IgE levels in allergic wild-type mice, IgE levels were undetectable in IL-4, IL-4R, and STAT6 KO mice, suggesting that IL-13 alone is not a switch factor for IgE synthesis in this model. These results illustrate the central role played by products derived from the COX pathway in the regulation of allergic immune responses.

This article has been cited by other articles:

				W. Zhou, D. C. Newcomb, M. L. Moore, K. Goleniewska, J. F. O'Neal, and R. S. Peebles Jr. Cyclooxygenase Inhibition during Allergic Sensitization Increases STAT6-Independent Primary and Memory Th2 Responses J. Immunol., October 15, 2008; 181(8): 5360 - 5367. [Abstract] [Full Text] [PDF]

				C. Feng, E. M. Beller, S. Bagga, and J. A. Boyce Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses Blood, April 15, 2006; 107(8): 3243 - 3250. [Abstract] [Full Text] [PDF]

				R. S. Peebles Jr, K. Hashimoto, J. R. Sheller, M. L. Moore, J. D. Morrow, S. Ji, J. A. Elias, K. Goleniewska, J. O'Neal, D. B. Mitchell, et al. Allergen-Induced Airway Hyperresponsiveness Mediated by Cyclooxygenase Inhibition Is Not Dependent on 5-Lipoxygenase or IL-5, but Is IL-13 Dependent J. Immunol., December 15, 2005; 175(12): 8253 - 8259. [Abstract] [Full Text] [PDF]

				K. Fukunaga, P. Kohli, C. Bonnans, L. E. Fredenburgh, and B. D. Levy Cyclooxygenase 2 Plays a Pivotal Role in the Resolution of Acute Lung Injury J. Immunol., April 15, 2005; 174(8): 5033 - 5039. [Abstract] [Full Text] [PDF]