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Critical Investigation of the CD14 Promoter Polymorphism: Lack of a Role for In Vitro Cytokine Response and Membrane CD14 Expression

By Sonja Van Aulock, Katja Gueinzius, Matthias Maass and Corinna Hermann

Abstract

Blood of volunteers, genotyped for the CD14 C(-159)-----+T polymorphism, showed no difference in cytokine release when stimulated with nine CD14-dependent immune stimuli. An analysis of the published data on the proposed association of CD14 genotype with membrane CD14 density revealed no significant correlation, questioning a functional impact of the CD14 polymorphism. Membrane-bound CD14 (mCDI4) recognizes bacterial compounds like lipopolysaccharide (LPS), Iipoteichoic acid (LTA), or peptidoglycan (PGN), while soluble CD14 (sCD14) mediates the response of endothelial and epithelial cells, which do not express CD14, to microbes. In 1999, a polymorphism of the cd14 gene within the promoter, CC-159)--+T [also referred to as CC-260)--+T], was described (2, 6, 14) and shown to be associated with a higher density of mCD14 (6) and higher sCD14 plasma concentrations (2). This was assumed to be the consequence of increased transcription of the CD14 gene in cases of the C-----+T substitution, but this hypothesis was so far supported only by the findings of LeVan et al., who showed changes in the binding of the transcription factors Sp1, Sp2, and Sp3 in the CD14 promoter (11). Furthermore, the T allele variant of CD14 was identified as a risk factor for myocardial infarction (6, 14). Using a standardized whole-blood assay (4), we investigated whether blood leukocytes of volunteers with the TT variant show stronger inflammatory responses than leukocytes from carriers of the CC genotype when stimulated with CD14-dependent stimuli. Heparinized blood from 160 healthy volunteers from th

Year: 2016
OAI identifier: oai:CiteSeerX.psu:10.1.1.950.4259
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