The whole-genome expression analysis of peripheral blood mononuclear cells from aspirin sensitive asthmatics versus aspirin tolerant patients and healthy donors after in vitro aspirin challenge.

Joanna Wieczfinska,Rafal Pawliczak,Milena Sokolowska,Piotr Kuna,Karolina Pospiech,Andrzej Bednarek,Izabela Kuprys–Lipinska,Magdalena Nowakowska,Dorota Kacprzak,Ewa Pniewska

doi:10.1186/s12931-015-0305-4

Joanna Wieczfinska, Rafal Pawliczak + Show 8 more

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https://doi.org/10.1186/s12931-015-0305-4

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Journal: Respiratory research	Publication Date: Dec 1, 2015
Citations: 86	License type: cc-by

Affiliation: Medical University of Lodz

Abstract

BackgroundUp to 30 % of adults with severe asthma are hypersensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients. Therefore, the aim of this study was to compare the AIA expression profile against aspirin tolerant asthma (ATA) and healthy volunteers (HV) profile in peripheral blood mononuclear cells (PBMCs) after in vitro aspirin challenge in Caucasian population.MethodsPBMCs were separated from blood of three groups of subjects - 11 AIA, 7 ATA and 15 HV and then stimulated by either 2 μM lysine aspirin or 20 μM lysine as a control. Subsequently, RNA was isolated, transcribed into cDNA and subjected to microarray and qPCR studies. Simultaneously, protein was extracted from PBMCs and used in further immunoblotting analysis.ResultsThe validation of results at mRNA level has shown only three genes, whose expression was significantly altered between comprising groups. mRNA expression of CNPY3 in PBMCs in AIA was significantly lower (-0.41 ± 2.67) than in HV (1.04 ± 2.69), (p = 0.02); mRNA expression of FOSL1 in PBMCs in AIA was also significantly decreased (-0.66 ± 2.97) as opposed to HV (0.31 ± 4.83), (p = 0.02). While mRNA expression of ERAS in PBMCs was increased (1.15 ± 0.23) in AIA in comparison to HV (-1.32 ± 0.41), (p = 0.03). At protein level the changed expression of one protein was confirmed. Protein expression of FOSL1 in PBMCs in AIA was both significantly lower (-0.86 ± 0.08) than in ATA (0.39 ± 0.42), (p = 0.046) and in HV (0.9 ± 0.27), (p = 0.007).ConclusionsThis pilot study implies a positive association between CNPY3, ERAS, FOSL1 and aspirin-intolerant asthma, suggesting that these findings would be useful for further investigations of NSAIDs mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0305-4) contains supplementary material, which is available to authorized users.

Highlights

Up to 30 % of adults with severe asthma are hypersensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients
Aspirin-exacerbated respiratory disease (AERD) is a distinct asthma phenotype mainly characterized by chronic eosinophilic inflammation of the upper and lower airways with symptoms that are exacerbated by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) [1,2,3,4]
It is estimated that 0.6–2.5 % of total population [5, 6], 5–10 % of asthmatic adults [7,8,9], almost 30 % adults with severe asthma [10] and just about 40 % of asthmatic adults with refractory chronic hyperplastic sinusitis [11] are hypersensitive to aspirin (ASA)

Summary

Introduction

Up to 30 % of adults with severe asthma are hypersensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients. Inhaled prostaglandin E2 (PGE2) inhibits aspirin - induced bronchoconstriction and cysLT production in subjects with AERD [17]. PGES-/- mice develop marked eosinophil - dominated bronchovascular cellular infiltrates with lesser numbers of neutrophiles [22, 23] and lysine aspirin (Lys-ASA) challenge caused additively releases of two markers of MC activation – histamine, mMCP-1 and cysLTs [21]. The marked depletion of residual PGE2 by Lys-ASA in the PGES-/mice suggests that mPGES-1 sustains PGE2 generation in the face of COX-1 inhibition [21]. It has been demonstrated that platelet- adherent eosinophils and neutrophils are more frequent in the peripheral blood and sinonasal tissues from patients with AERD than in samples from aspirin tolerant controls [24]. Though the residual local PGE2 derives principally from COX-1, which may explain why only COX-1 – active drugs provoke clinical reactions [27]

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