title: The β2-adrenoreceptor gene promoter polymorphisms may modulate β2-agonist- and glucocorticoid-induced IgE synthesis.
abstract: BACKGROUND
  β2-adrenoreceptor (β2-AR) agonists and glucocorticoids (GCS) were shown to induce IgE synthesis in human PBMCs. Serum total IgE levels are associated with single nucleotide polymorphisms (SNPs) of the β2-AR gene. We aimed to assess the association of the effect of fenoterol (β2-AR agonist) on IL-4-driven and budesonide-induced IgE synthesis with genetic variants of β2-AR.
  
  
  METHODS
  The study included 25 individuals: 13 with allergic asthma and/or allergic rhinitis and 12 healthy volunteers. PBMCs were cultured with IL-4, fenoterol and/or budesonide, and IgE concentrations in supernatants were assessed. Five SNPs in positions: -47, -20, 46, 79 and 252 of β2-AR were determined by direct DNA sequencing.
  
  
  RESULTS
  In -47 T/T and -20 T/T patients, incubation with fenoterol resulted in decreased IgE production, whereas in -47 C/T and -47 C/C as well as in -20 C/T and -20 C/C individuals, it was enhanced. In contrast to fenoterol, budesonide-induced IgE synthesis was significantly increased in -47 T/T and -20 T/T patients as compared to -47 C/T, -47 C/C, -20 C/T and -47 C/C individuals. Polymorphisms in positions 46, 79 and 252 were not associated with fenoterol- or budesonide-modulated IgE synthesis. No differences in the distribution of IgE synthesis was seen between atopic and non-atopic individuals carrying the same alleles.
  
  
  CONCLUSIONS
  The differential effect of β2-agonists and GCS on IgE synthesis may be associated with genetic variants of promoter region of the β2-AR gene.
authors.affiliation: Department of Immunology, Rheumatology and Allergy, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. Electronic address: mchalubinski@op.pl.
authors.forename: M
authors.initials: M
authors.lastname: Chalubinski
authors.affiliation: Department of Microbiology and Laboratory Medical Immunology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Grzegorczyk
authors.affiliation: Department of Microbiology and Laboratory Medical Immunology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Grzelak
authors.affiliation: Department of Immunology, Rheumatology and Allergy, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Jarzebska
authors.affiliation: Department of Immunology, Rheumatology and Allergy, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: M L
authors.initials: ML
authors.lastname: Kowalski
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D000917:Antibody Formation / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D005280:Fenoterol / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D065631:Rhinitis, Allergic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D015847:Interleukin-4; D005280:Fenoterol; D007073:Immunoglobulin E; D019819:Budesonide
keywords: Asthma; Glucocorticoids; IgE; β2-Adrenoreceptor; β2-Agonists