Abstract | BACKGROUND: Regulation of prostaglandin synthesis and the activation of human airway fibroblasts associated with the remodeling of the bronchi play an important role in asthma. OBJECTIVE: METHODS: Generation of prostaglandin E(2) ( PGE(2)) and pros-taglandin D(2) ( PGD(2)) by bronchial fibroblasts was measured by means of mass spectrometry in culture supernatants, and cyclooxgenases expression was estimated by means of RT-PCR and immunoblotting. The cells were isolated from 3 groups of subjects: nonasthmatic patients (n = 10), patients with aspirin-tolerant asthma (ATA, n = 9), and patients with aspirin-intolerant asthma (AIA, n = 7). RESULTS: The cytomix (LPS, 5 square g/mL; IL-1 square, 5 ng/mL; and TNF- square, 10 ng/mL; 18 hours) stimulated the production of prostaglandins. Asthmatic patients were characterized by low capacity to produce PGE(2) after cytomix stimulation. In the nonasthmatic patient group the mean PGE(2) production was 32 +/- 33 ng/mL (35-fold of the basic production), in the ATA group it was 16 +/- 18 ng/mL (16-fold), and in the AIA group it was only 5.3 +/- 3.6 ng/mL (4-fold). The mean concentration of PGD(2) for nonasthmatic patients, patients with ATA, and patients with AIA was 0.18 +/- 0.16 ng/mL (4.7-fold of the basic production), 0.18 +/- 0.14 ng/mL (4.2-fold), and 0.235 +/- 0.19 ng/mL (1.9-fold), respectively. The observed difference was not due to insufficient cyclooxygenase 2 expression because all groups had similar levels of its mRNA and protein. The patients with AIA had low expression levels of cyclooxygenase 1 protein but not of its mRNA. The PGE(2)/ PGD(2) concentration ratio increased after cytomix stimulation in all groups but was significantly less in patients with AIA than in patients with ATA. CONCLUSIONS: Our results point to a deficient PGE(2) production under proinflammatory conditions in asthmatic airways. This could weaken local defensive mechanisms and promote cysteinyl leukotriene overproduction.
|
Authors | Malgorzata Pierzchalska, Zsuzsanna Szabó, Marek Sanak, Jerzy Soja, Andrzej Szczeklik |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 111
Issue 5
Pg. 1041-8
(May 2003)
ISSN: 0091-6749 [Print] United States |
PMID | 12743569
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Isoenzymes
- Membrane Proteins
- Cyclooxygenase 1
- Cyclooxygenase 2
- PTGS1 protein, human
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
- Dinoprostone
- Aspirin
- Prostaglandin D2
- Indomethacin
|
Topics |
- Adult
- Aged
- Aspirin
(adverse effects)
- Asthma
(chemically induced, metabolism)
- Bronchi
(metabolism)
- Cells, Cultured
- Cyclooxygenase 1
- Cyclooxygenase 2
- Dinoprostone
(biosynthesis)
- Female
- Fibroblasts
(metabolism)
- Humans
- Indomethacin
(pharmacology)
- Isoenzymes
(biosynthesis)
- Male
- Membrane Proteins
- Middle Aged
- Prostaglandin D2
(biosynthesis)
- Prostaglandin-Endoperoxide Synthases
(biosynthesis)
|