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Myeloid differentiation 2 as a therapeutic target of inflammatory disorders.

Abstract
Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, activates the innate immunity system through a receptor complex of myeloid differentiation 2 (MD-2) and toll-like receptor 4 (TLR4). MD-2 directly recognizes the lipid A domain of LPS, which triggers MD-2/TLR4-mediated cellular response aimed at eliminating the invaded pathogen. However, excess production of inflammatory mediators is harmful to host tissue and this can cause septic death in extreme cases. MD-2 represents an attractive therapeutic target of inflammatory and immune diseases in human. In particular, eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site, and it ameliorates various inflammatory conditions due to infection or sterile organ injury. In this review, we outline the recent advances in the structure biology of ligand interaction with MD-2/TLR4, and highlight the MD-2-directed LPS antagonists, which are natural and synthetic chemicals, under development to treat inflammatory diseases.
AuthorsSun Hong Park, Nam Doo Kim, Jae-Kyung Jung, Chong-Kil Lee, Sang-Bae Han, Youngsoo Kim
JournalPharmacology & therapeutics (Pharmacol Ther) Vol. 133 Issue 3 Pg. 291-8 (Mar 2012) ISSN: 1879-016X [Electronic] England
PMID22119168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Disaccharides
  • Glycolipids
  • Lipid A
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Sugar Phosphates
  • Toll-Like Receptor 4
  • lipid A precursors, bacterial
  • eritoran
Topics
  • Animals
  • Anti-Inflammatory Agents (therapeutic use)
  • Disaccharides (therapeutic use)
  • Glycolipids (therapeutic use)
  • Humans
  • Inflammation (drug therapy, immunology)
  • Lipid A (analogs & derivatives, therapeutic use)
  • Lipopolysaccharides (immunology)
  • Lymphocyte Antigen 96 (agonists, antagonists & inhibitors, immunology)
  • Sugar Phosphates (therapeutic use)
  • Toll-Like Receptor 4 (immunology)

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