title: The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma.
abstract: BACKGROUND
  Even though the genotype at the promoter region of the CD14 molecule is known to affect the atopic phenotypes, the cellular and molecular basis of this association is largely unknown.
  
  
  OBJECTIVE
  To investigate the effect of lipopolysaccharide (LPS) on IgE production and cytokine profile by peripheral blood mononuclear cells (PBMC) obtained from asthmatic children with the TT and the CC genotypes at position -159 of the CD14 gene.
  
  
  METHODS
  Peripheral blood mononuclear cells from asthmatic children with alternative genotypes at CD14 C159T locus were stimulated with 2 and 200 ng/ml LPS in vitro. The IgE, IgG and, IgM response was determined by ELISA and Ig έ-germline, IgG, and IgM transcription by real-time PCR. A cluster of cytokines was measured by cytometric bead array.
  
  
  RESULTS
  Asthmatic children with the TT genotype but not those with the CC genotype responded with increased IgE synthesis and germline transcription to LPS stimulation. There were no genotype-related differences in IgG and IgM. TT but not the CC genotype was associated with significantly increased interleukin (IL)-4/IL-12 and IL-4/interferon-gamma (IFN-γ) ratios in the culture supernatant. There were no genotype-related differences in IL-1β, IL-7, IL-10, IL-13, IL-17A, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein, and tumor necrosis factor alpha.
  
  
  CONCLUSIONS
  Peripheral blood mononuclear cells from asthmatic children with the TT genotype at position -159 of the CD14 gene make more IgE than those with the CC genotype following LPS stimulation because of increased germline transcription and have an augmented Th2 cytokine profile.
authors.affiliation: Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Hacettepe, Ankara, Turkey. csackesen@yahoo.com
authors.forename: C
authors.initials: C
authors.lastname: Sackesen
authors.forename: E
authors.initials: E
authors.lastname: Birben
authors.forename: O U
authors.initials: OU
authors.lastname: Soyer
authors.forename: U M
authors.initials: UM
authors.lastname: Sahiner
authors.forename: T S
authors.initials: TS
authors.lastname: Yavuz
authors.forename: E
authors.initials: E
authors.lastname: Civelek
authors.forename: E
authors.initials: E
authors.lastname: Karabulut
authors.forename: M
authors.initials: M
authors.lastname: Akdis
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
authors.forename: O
authors.initials: O
authors.lastname: Kalayci
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D007073:Immunoglobulin E