TY - JOUR
T1 - Association between CD14 polymorphisms and serum soluble CD14 levels
T2 - Effect of atopy and endotoxin inhalation
AU - LeVan, Tricia D.
AU - Michel, Olivier
AU - Dentener, Mieke
AU - Thorn, Jörgen
AU - Vertongen, Francoise
AU - Beijer, Lena
AU - Martinez, Fernando D.
N1 - Funding Information:
Supported by grants from the National Institutes of Health (ES-00386 to T.D.L. and HL61892 to F.D.M.), the American Heart Association (9960342Z to T.D.L.), and Astra Zeneca Belgium (to O.M.).
PY - 2008/2
Y1 - 2008/2
N2 - Background: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. Objective: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. Methods: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 μg of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. Results: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. Conclusion: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels.
AB - Background: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. Objective: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. Methods: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 μg of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. Results: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. Conclusion: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels.
KW - CD14 antigen
KW - atopy
KW - endotoxin
KW - exposure
KW - inflammation
KW - innate immunity
KW - lipopolysaccharide
KW - single nucleotide polymorphism
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U2 - 10.1016/j.jaci.2007.08.050
DO - 10.1016/j.jaci.2007.08.050
M3 - Article
C2 - 17949800
AN - SCOPUS:38949193248
SN - 0091-6749
VL - 121
SP - 434-440.e1
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -