IL-10 release requires stronger toll-like receptor 4-triggering than TNF: a possible explanation for the selective effects of heterozygous TLR4 polymorphism Asp(299)Gly on IL-10 release

Immunobiology. 2008;213(8):621-7. doi: 10.1016/j.imbio.2008.03.001. Epub 2008 May 23.

Abstract

The toll-like receptor 4 Asp(299)Gly polymorphism results in an inactive receptor. Heterozygosis is associated with reduced LPS-inducible IL-10 protein and IL-10 mRNA from blood leukocytes and isolated monocytes, while numerous other mediators are not affected. We could exclude that this effect is due to the differences in the kinetics of IL-10 release, in the expression of total surface TLR4 or in LPS-binding to monocytes between subjects heterozygous for the Asp(299)Gly polymorphism or homozygous carriers of the wild-type allele. Furthermore, we could show that IL-10 induction in general requires stronger LPS-triggering than TNF and is more sensitive to LPS inhibitors. The lower number of responsive wild-type TLR4 receptors on monocytes of heterozygotes may explain why only IL-10 release is affected.

MeSH terms

  • Alleles
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Immunity, Innate
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism*
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / analysis
  • Signal Transduction / immunology
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Lipopolysaccharides
  • RNA, Messenger
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interleukin-10