Published ahead of print on March 5, 2003, doi:10.1164/rccm.200211-1383OC
Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1509-1515
A more recent version of this article appeared on June 1, 2003
Submitted on November 27, 2002
Accepted on March 4, 2003
Accentuated TH2 airway response after allergen challenge in COX-1-/- but not COX-2-/- mice
Michelle A Carey1, Dori R Germolec1, J. Alyce Bradbury1, Rebecca A Gooch1, Michael P Moorman1, Gordon P Flake1, Robert Langenbach1, and Darryl C Zeldin1*
1 Division of Intramural Research, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
* To whom correspondence should be addressed. E-mail: zeldin{at}niehs.nih.gov.
Acute pharmacological inhibition of cyclooxygenase-1 or -2 during allergen sensitization and exposure leads to enhanced Th2 airway responses. Cyclooxygenase-1 and -2 play functionally distinct roles in lymphocyte development and consequently genetic deficiency of either enzyme, as opposed to acute pharmacological inhibition, may modulate Th2 mediated allergic airway disease differently. An ovalbumin-induced mouse model of allergic airway disease was used. The immunophenotype of bronchoalveolar lavage lymphocytes was assessed by flow cytometry, bronchoalveolar lavage cytokines and chemokines were measured by enzyme-linked immunosorbent assay, adhesion molecule expression was assessed by immunoblotting in combination with immunohistochemistry, and bronchoconstriction was assessed by whole body plethysmography. The airways of Cyclooxygenase-1-/- mice contained increased numbers of CD4+ and CD8+ T cells, exaggerated levels of the Th2 cytokines interleukin-4, -5 and -13 and increased levels of eotaxin and thymus and activation-regulated chemokine. Allergen-induced bronchoconstriction was also increased in Cyclooxygenase-1-/- mice. Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 levels were increased in lungs of both Cyclooxygenase-1-/- and Cyclooxygenase-2-/- mice relative to wild type. These data suggest that genetic deficiency of Cyclooxygenase-1 but not Cyclooxygenase-2 modulates T cell recruitment, Th2 cytokine secretion and lung function in the allergic airway.
Key words: Cyclooxygenase, Th2 Cytokine, Ovalbumin
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]
|
|
|
|
|
|
|
S. M. Saleh, T. S. Mann, T. Peters, R. J. Betts, and P. J. Henry
Influence of Dexamethasone on Protease-Activated Receptor 2-Mediated Responses in the Airways
J. Pharmacol. Exp. Ther.,
February 1, 2008;
324(2):
622 - 630.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Carey, J. W. Card, J. A. Bradbury, M. P. Moorman, N. Haykal-Coates, S. H. Gavett, J. P. Graves, V. R. Walker, G. P. Flake, J. W. Voltz, et al.
Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-{alpha}-deficient Mice
Am. J. Respir. Crit. Care Med.,
January 15, 2007;
175(2):
126 - 135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Card, M. A. Carey, J. A. Bradbury, J. P. Graves, F. B. Lih, M. P. Moorman, D. L. Morgan, L. M. DeGraff, Y. Zhao, J. F. Foley, et al.
Cyclooxygenase-1 Overexpression Decreases Basal Airway Responsiveness but Not Allergic Inflammation
J. Immunol.,
October 1, 2006;
177(7):
4785 - 4793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Witzenrath, B. Ahrens, S. M. Kube, A. Braun, H. G. Hoymann, A. C. Hocke, S. Rosseau, N. Suttorp, E. Hamelmann, and H. Schutte
Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs
Am J Physiol Lung Cell Mol Physiol,
September 1, 2006;
291(3):
L466 - L472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kanefsky, M. Lenburg, and C.-M. Hai
Cholinergic Receptor and Cyclic Stretch-Mediated Inflammatory Gene Expression in Intact ASM
Am. J. Respir. Cell Mol. Biol.,
April 1, 2006;
34(4):
417 - 425.
[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]
|
|
|
|
|
|
|
M. A. Carey, J. A. Bradbury, J. M. Seubert, R. Langenbach, D. C. Zeldin, and D. R. Germolec
Contrasting Effects of Cyclooxygenase-1 (COX-1) and COX-2 Deficiency on the Host Response to Influenza A Viral Infection
J. Immunol.,
November 15, 2005;
175(10):
6878 - 6884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Murakami, S. Masuda, K. Ueda-Semmyo, E. Yoda, H. Kuwata, Y. Takanezawa, J. Aoki, H. Arai, H. Sumimoto, Y. Ishikawa, et al.
Group VIB Ca2+-independent Phospholipase A2{gamma} Promotes Cellular Membrane Hydrolysis and Prostaglandin Production in a Manner Distinct from Other Intracellular Phospholipases A2
J. Biol. Chem.,
April 8, 2005;
280(14):
14028 - 14041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Zeytin, A. C. Patel, C. J. Rogers, D. Canter, S. D. Hursting, J. Schlom, and J. W. Greiner
Combination of a Poxvirus-Based Vaccine with a Cyclooxygenase-2 Inhibitor (Celecoxib) Elicits Antitumor Immunity and Long-Term Survival in CEA.Tg/MIN Mice
Cancer Res.,
May 15, 2004;
64(10):
3668 - 3678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2003
Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
265 - 276.
[Full Text]
[PDF]
|
|
|
Copyright © 2003 American Thoracic Society
|
|
|
