Role of MD-2 in TLR2- and TLR4-mediated recognition of Gram-negative and Gram-positive bacteria and activation of chemokine genes

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

MD-2 is associated with TLR4 on the cell surface and enables TLR4 to respond to LPS. TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS, ReLPS, and lipid A. MD-2 enables TLR2 to respond to non-activating LPS, ReLPS, and lipid A, and enhances TLR2-mediated responses to Gram-negative and Gram-positive bacteria, protein-containing LPS, peptidoglycan, and lipoteichoic acid. MD-2 enables TLR4 to respond to a wide variety of endotoxic LPS partial structures, Gram-negative bacteria, and Gram-positive lipoteichoic acid, but not to Gram-positive bacteria, peptidoglycan, and lipopeptide. MD-2 physically associates with both TLR4 and TLR2, but the association with TLR2 is weaker than with TLR4. Also, MD-2 and TLR2 and TLR4 enhance each other's expression. The highest induced genes in human monocytes stimulated with Gram-positive and Gram-negative bacterial cell wall components are chemokine genes, and IL-8 is the highest induced chemokine. Both Gram-positive and Gram-negative bacteria activate TLR2→ MyD88→IRAK→TRAF→NIK→IKK→NF-κB signal transduction pathway that induces transcription of the IL-8 gene. Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8.

Original languageEnglish (US)
Pages (from-to)401-405
Number of pages5
JournalJournal of Endotoxin Research
Volume6
Issue number5
DOIs
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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