Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma

Pierzchalska, Małgorzata; Szabó, Zsuzsanna; Sanak, Marek; Soja, Jerzy; Szczeklik, Andrzej

doi:10.1067/mai.2003.1491

Cited by 127 publications

(155 citation statements)

References 38 publications

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“…Similarly, other studies have also shown a significantly low production of PGE 2 in cultured bronchial fibroblasts from AIA [13].…”

Section: Discussionmentioning

confidence: 95%

“…In patients with asthma, and especially in AIA, various data support the existence of an altered regulation of the COX pathway [9][10][11][12][13][14][15]. PGE 2 levels have been reported to be low in the nasal polyps of asthma patients, as well as in nasal-polyp and bronchial fibroblasts from asthmatic patients, particularly those with aspirin sensitivity [11,[13][14][15]. As PGE 2 production mostly depends on the level of COX-2 induction under conditions of inflammation, it should be expected that the low production of PGE 2 detected in asthma and nasal polyps would be accompanied by a similar, concomitant alteration in the expression of COX-2.…”

Section: Introductionmentioning

confidence: 99%

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Fatty Acid Composition of Cultured Fibroblasts Derived from Healthy Nasal Mucosa and Nasal Polyps

2016

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Abstract:Background: Fibroblasts from nasal polyps (NP) of asthma patients have reduced expression of cyclooxygenase 2 (COX-2) and production of prostaglandin E 2 (PGE 2 ). We hypothesized that the reported alterations are due to alterations in the availability of arachidonic acid (AA). Objective: The objective was to determine the fatty acid composition of airway fibroblasts from healthy subjects and from asthma patients with and without aspirin intolerance. Methods: We analyzed the fatty acid composition of cultured fibroblasts from non-asthmatics (n = 6) and from aspirin-tolerant (n = 6) and aspirin-intolerant asthmatics (n = 6) by gas chromatography-flame ionization detector. Fibroblasts were stimulated with acetyl salicylic acid (ASA). Results: The omega-6 fatty acids dihomo-gamma-linolenic acid (C20:3) and AA (C20:4), and omega-3 fatty acids docosapentaenoic acid (DPA) (C22:5) and docosahexaenoic acid (DHA) (C22:6) were significantly higher in NP fibroblasts than in fibroblasts derived from nasal mucosa. The percentage composition of the fatty acids palmitic acid (C16:0) and palmitoleic acid (C16:1) was significantly higher in fibroblasts from patients with NP and aspirin intolerance than in fibroblasts derived from the nasal NP of aspirin-tolerant patients. ASA did not cause changes in either omega-3 or omega-6 fatty acids. Conclusions. Our data do not support the hypothesis that a reduced production of AA in NP fibroblasts can account for the reported low production of PGE 2 in nasal polyps. Whether the increased proportion of omega-3 fatty acids can contribute to reduced PGE 2 production in nasal polyps by competitively inhibiting COX-2 and reducing the amount of AA available to the COX-2 enzyme remains to be elucidated.

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“…Similarly, other studies have also shown a significantly low production of PGE 2 in cultured bronchial fibroblasts from AIA [13].…”

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Fatty Acid Composition of Cultured Fibroblasts Derived from Healthy Nasal Mucosa and Nasal Polyps

2016

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“…Although the underlying mechanisms of AIA have not been elucidated completely, arachidonic acid metabolites such as prostaglandins (PGs), leukotrienes (LTs), and thromboxane (TBX) are reportedly involved in the pathogenesis of this asthma phenotype (8)(9)(10). Anti-inflammatory PGs are one of the various types of oxygenated metabolites generated by the cyclooxygenase (COX) pathway that function to reduce the level of PGE2, the main COX2 metabolite (11)(12)(13). The cyclooxygenase theory is widely accepted as responsible for the pathogenesis of AIA.…”

Section: Introductionmentioning

confidence: 99%

Association of PTGER gene family polymorphisms with aspirin intolerant asthma in Korean asthmatics

Park

Park²,

Park³

et al. 2010

BMB Reports

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“…2,4 Overproduction of CysLTs and deficiency of prostaglandin E 2 in bronchial fibroblasts by COX inhibition have been proposed to have crucial roles in AERD development. 4,15 However, along with conflicting results for the associations between polymorphisms of genes in leukotriene and COX pathways [16][17][18] genes on other pathways including bronchial hyperresponsiveness by MHC or structural genes have provided new insights for AERD pathogenesis. 5,19 Therefore, although further replications and functional evaluations are required, our findings on the associations of TAP2 with AERD-related symptoms, particularly with FEV1 decline by aspirin provocation, might provide evidences for the role of the gene in respiratory deficiencies.…”

Section: Discussionmentioning

confidence: 99%

Genetic association analysis of TAP1 and TAP2 polymorphisms with aspirin exacerbated respiratory disease and its FEV1 decline

et al. 2011

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Aspirin exacerbated respiratory disease (AERD) induces bronchoconstriction in asthmatic patients characterized with a clinical condition of severe decline in forced expiratory volume in one second (FEV1) after ingestion of aspirin. Two genes consisting a heterodimer, transporter 1 and 2, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1 and TAP2) within the major histocompatibility complex (MHC) region, have been implicated in immunodeficiency and bronchiectasis development. To investigate the associations of TAP1 and TAP2 genetic polymorphisms with AERD and phenotypic FEV1 decline, a total of 43 common single-nucleotide polymorphisms (SNPs) including 12 SNPs of TAP1 and 31 SNPs of TAP2 were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma controls. Interestingly, regression analysis revealed that polymorphisms and haplotypes of TAP2 were associated with FEV1 decline by aspirin provocation (P¼0.002-0.04), with about twofold decline rate of FEV1 in most of minor homozygotes compared with major homozygotes. In addition, nominal evidences of association between TAP2 and AERD development were observed (P¼0.02-0.04). However, TAP1 polymorphisms showed no relations to both AERD and FEV1 decline after aspirin challenge (P40.05). Although further functional evaluations and replications are required, our preliminary findings provide supporting information that variants of TAP2 might be predisposing factors for FEV1 decline-related symptoms.

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Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma

Abstract: 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.

Cited by 127 publications

References 38 publications

Fatty Acid Composition of Cultured Fibroblasts Derived from Healthy Nasal Mucosa and Nasal Polyps

Fatty Acid Composition of Cultured Fibroblasts Derived from Healthy Nasal Mucosa and Nasal Polyps

Association of PTGER gene family polymorphisms with aspirin intolerant asthma in Korean asthmatics

Genetic association analysis of TAP1 and TAP2 polymorphisms with aspirin exacerbated respiratory disease and its FEV1 decline

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