Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma - 29/08/11
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: We sought to assess the cyclooxygenase pathways in airway fibroblasts of patients with bronchial asthma. Methods: Generation of prostaglandin E2 (PGE2) and pros-taglandin D2 (PGD2) 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 □g/mL; IL-1□, 5 ng/mL; and TNF-□, 10 ng/mL; 18 hours) stimulated the production of prostaglandins. Asthmatic patients were characterized by low capacity to produce PGE2 after cytomix stimulation. In the nonasthmatic patient group the mean PGE2 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 PGD2 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 PGE2/PGD2 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 PGE2 production under proinflammatory conditions in asthmatic airways. This could weaken local defensive mechanisms and promote cysteinyl leukotriene overproduction. (J Allergy Clin Immunol 2003;111:1041-8.)
Le texte complet de cet article est disponible en PDF.Keywords : Asthma, aspirin-induced asthma, human bronchial fibroblasts, prostaglandins, cyclooxygenase 1, cyclooxygenase 2
Abbreviations : AIA, ATA, BAL, CT, DMEM, HBF, mPGES, NSAID, PGD2, PGE2
Plan
 | Both authors contributed to the work equally. |
| Supported by the Polish State Committee for Scientific Research grant no. 6 PO5B 140 21. MP's visit to Southampton was supported by a travel award from the Wellcome Trust. Z.S.'s stay at the University Department of Medicine in Krakow was supported by a scholarship from the Hungarian Pulmonological Foundation. |
 | Reprint requests: Andrzej Szczeklik, MD, Department of Medicine, Jagellonian University Medical School, 8. Skawin ́ska Str, 31-066 Cracow, Poland. |
Vol 111 - N° 5
P. 1041-1048 - mai 2003 Retour au numéro
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