A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity

J Immunol. 2001 Nov 15;167(10):5838-44. doi: 10.4049/jimmunol.167.10.5838.


CD14 is a pattern recognition receptor that plays a central role in innate immunity through recognition of bacterial lipoglycans, primarily LPS. Recently, our group has identified a common single nucleotide polymorphism, -159C-->T, in the CD14 proximal promoter. Homozygous carriers of the T allele have a significant increase in soluble CD14, but a decreased total serum IgE. This epidemiologic evidence led us to investigate the molecular basis for the effects of CD14/-159C-->T on CD14 regulation in monocytes and hepatocytes, the two major cell types known to express this gene in vivo. EMSA analysis showed that the T allele results in decreased affinity of DNA/protein interactions at a GC box that contains a binding site for Sp1, Sp2, and Sp3 transcription factors. In reporter assays, the transcriptional activity of the T allele was increased in monocytic Mono Mac 6 cells, which express low levels of Sp3, a member of the Sp family with inhibitory potential relative to activating Sp1 and Sp2. By contrast, both alleles were transcribed equivalently in Sp3-rich hepatocytic HepG2 cells. Our data indicate that the interplay between CD14 promoter affinity and the [Sp3]:[Sp1 + Sp2] ratio plays a critical mechanistic role in regulating transcription of the two CD14 alleles. Variation in a key gene of innate immunity may be important for the pathogenesis of allergy and inflammatory disease through gene-by-gene and/or gene-by-environment interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • GC Rich Sequence
  • Genes, Reporter
  • HeLa Cells
  • Hepatocytes / metabolism
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Molecular Sequence Data
  • Monocytes / metabolism
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Sp1 Transcription Factor / metabolism*
  • Sp2 Transcription Factor
  • Sp3 Transcription Factor
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • DNA-Binding Proteins
  • Lipopolysaccharide Receptors
  • SP2 protein, human
  • SP3 protein, human
  • Sp1 Transcription Factor
  • Transcription Factors
  • Sp2 Transcription Factor
  • Sp3 Transcription Factor