|
|
||||||||||||||
|
|
|||||||||||||||
a University Medicine,
Southampton General Hospital, Tremona Road, Southampton SO16 6YD,
UK, b Department of Histochemistry, Imperial College
School of Medicine, Hammersmith Hospital, London W12 0NN, UK, c Department of Infectious Diseases, Imperial
College School of Medicine, d CEA,
SPI/DRM, Bâtiment 136, CEA-Saclay, 91191 Gif-sur-Yvette, Cedex,
France, e U348 INSERM,
Hôpital Lariboisière, 8 rue Patin, 75475 Paris Cedex 10, France
Correspondence to: Dr A E Redington, Academic Department of Medicine, Castle Hill Hospital, Castle Road, Cottingham, East Yorkshire HU16 5JQ, UK a.e.redington{at}medschool.hull.ac.uk
Received 14 September 2000; Returned to authors 2 December 2000; Revised version received 19 January 2001; Accepted for publication 22 January 2001
BACKGROUND
Nitric
oxide (NO) and prostanoids are mediators of vascular and bronchial tone
that are postulated to be involved in asthma. Increased levels of both
are found in asthmatic subjects and are synthesised by enzymes that
have cytokine inducible forms: inducible NO synthase (iNOS) and
cyclo-oxygenase-2 (COX-2), respectively. We hypothesised that the in
vivo expression of iNOS and COX-2 in the airways would be increased in
asthma, and that these cytokine inducible enzymes may represent targets
for regulation by corticosteroid treatment.
METHODS
Bronchial
biopsy specimens were obtained from three groups of subjects: atopic
asthmatics treated with
2 agonists alone (n=7), atopic
asthmatics additionally receiving regular treatment with corticosteroids (n=8), and non-asthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and immunoreactive protein was studied using in situ hybridisation and quantitative immunohistochemistry.
RESULTS
Immunoreactivity
and the hybridisation signal for iNOS and COX-2 were mainly localised
in the airway epithelium. The proportion of epithelium immunostained
was significantly greater in the non-steroid treated asthmatic subjects
(iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid treated
asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or
the non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003). Similarly, the hybridisation signal was stronger in
the non-steroid treated group of asthmatic subjects than in the other
two groups.
CONCLUSIONS
These
findings highlight the potential role of the airway epithelium both as
a contributor to the inflammatory process in asthma and as a target for
inhaled corticosteroid treatment in this disease.
This article has been cited by other articles:
![]() |
J. M. Owens, K. R. Shroyer, and T. T. Kingdom Expression of Cyclooxygenase and Lipoxygenase Enzymes in Sinonasal Mucosa of Patients With Cystic Fibrosis Arch Otolaryngol Head Neck Surg, August 1, 2008; 134(8): 825 - 831. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Takemoto, K. Ogino, M. Shibamori, T. Gondo, Y. Hitomi, T. Takigawa, D.-H. Wang, J. Takaki, H. Ichimura, Y. Fujikura, et al. Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1419 - L1426. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Owens, K. R. Shroyer, and T. T. Kingdom Expression of cyclooxygenase and lipoxygenase enzymes in nasal polyps of aspirin-sensitive and aspirin-tolerant patients. Arch Otolaryngol Head Neck Surg, June 1, 2006; 132(6): 579 - 587. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Tsoumakidou, E. Papadopouli, N. Tzanakis, and N. M. Siafakas Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma Chest, May 1, 2006; 129(5): 1194 - 1202. [Abstract] [Full Text] [PDF] |
||||
![]() |
ATS Workshop Proceedings: Exhaled Nitric Oxide and Nitric Oxide Oxidative Metabolism in Exhaled Breath Condensate. Proceedings of the ATS, January 1, 2006; 3(2): 131 - 145. [Full Text] [PDF] |
||||
![]() |
J C Ojoo, S A Mulrennan, J A Kastelik, A H Morice, and A E Redington Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis Thorax, January 1, 2005; 60(1): 22 - 26. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-W. Shin, C. M. Rose-Gottron, D. M. Cooper, R. L. Newcomb, and S. C. George Airway diffusing capacity of nitric oxide and steroid therapy in asthma J Appl Physiol, January 1, 2004; 96(1): 65 - 75. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. S. Chambers, J. L. Black, Q. Ge, S. M. Carlin, W. W. Au, M. Poniris, J. Thompson, P. R. Johnson, and J. K. Burgess PAR-2 activation, PGE2, and COX-2 in human asthmatic and nonasthmatic airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L619 - L627. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Huszar, G. Vass, E. Vizi, Zs. Csoma, E. Barat, Gy. Molnar Vilagos, I. Herjavecz, and I. Horvath Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma Eur. Respir. J., December 1, 2002; 20(6): 1393 - 1398. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. E. Marik and G. P. Zaloga Adrenal Insufficiency in the Critically Ill: A New Look at an Old Problem Chest, November 1, 2002; 122(5): 1784 - 1796. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Schwingshackl, R. Moqbel, and M. Duszyk Nitric oxide activates ATP-dependent K+ channels in human eosinophils J. Leukoc. Biol., May 1, 2002; 71(5): 807 - 812. [Abstract] [Full Text] [PDF] |
||||
![]() |
L PANG COX-2 expression in asthmatic airways: the story so far Thorax, May 1, 2001; 56(5): 335 - 336. [Full Text] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |