title: 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.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  PBMCs 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Immunopathology, Medical University of Lodz, Chair of Allergology, Immunology and Dermatology, 7/9 Zeligowskiego, 90-752, Lodz, Poland. joanna.wieczfinska@umed.lodz.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wieczfinska
authors.affiliation: Department of Immunopathology, Medical University of Lodz, Chair of Allergology, Immunology and Dermatology, 7/9 Zeligowskiego, 90-752, Lodz, Poland. dorkac@csk.umed.lodz.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kacprzak
authors.affiliation: Department of Molecular Carcinogenesis, Medical University of Lodz, Chair of Molecular Medicine and Biotechnology, Lodz, Poland. karolina.pospiech@umed.lodz.pl.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pospiech
authors.affiliation: Department of Immunopathology, Medical University of Lodz, Chair of Allergology, Immunology and Dermatology, 7/9 Zeligowskiego, 90-752, Lodz, Poland. milena.sokolowska@siaf.uzh.ch.|Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland. milena.sokolowska@siaf.uzh.ch.
authors.forename: Milena
authors.initials: M
authors.lastname: Sokolowska
authors.affiliation: Department of Molecular Carcinogenesis, Medical University of Lodz, Chair of Molecular Medicine and Biotechnology, Lodz, Poland. magdalena.nowakowska@umed.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Nowakowska
authors.affiliation: Department of Immunopathology, Medical University of Lodz, Chair of Allergology, Immunology and Dermatology, 7/9 Zeligowskiego, 90-752, Lodz, Poland. e.pniewska@csk.umed.lodz.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pniewska
authors.affiliation: Department of Molecular Carcinogenesis, Medical University of Lodz, Chair of Molecular Medicine and Biotechnology, Lodz, Poland. andrzej.bednarek@umed.lodz.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bednarek
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz, Poland. izabela.kuprys-lipinska@umed.lodz.pl.
authors.forename: Izabela
authors.initials: I
authors.lastname: Kuprys-Lipinska
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz, Poland. piotr.kuna@umed.lodz.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
authors.affiliation: Department of Immunopathology, Medical University of Lodz, Chair of Allergology, Immunology and Dermatology, 7/9 Zeligowskiego, 90-752, Lodz, Poland. rafal.pawliczak@umed.lodz.pl.
authors.forename: Rafal
authors.initials: R
authors.lastname: Pawliczak
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D055963:Asthma, Aspirin-Induced / Q000235:genetics*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D010865:Pilot Projects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results; D055815:Young Adult; D000099169:Fos-Related Antigen 1
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D018076:DNA, Complementary; D015689:Oncogene Protein p21(ras); D016760:Proto-Oncogene Proteins c-fos; D012313:RNA; D000099169:Fos-Related Antigen 1; C474774:ERas protein, human