The role of NLRs and TLRs in the activation of the inflammasome

Expert Opin Biol Ther. 2008 Dec;8(12):1867-72. doi: 10.1517/14712590802494212.

Abstract

Background: Interleukin-1 beta is one of the most important pro-inflammatory cytokines. In contrast to other cytokines, activation of IL-1 beta requires processing from an inactive precursor by the cysteine protease caspase-1. Caspase-1 forms a protein platform called the inflammasome, together with proteins of the nucleotide-binding oligomerization domain-like receptor (NLR) family.

Objective/methods: A review of literature investigating the stimulation of IL-1 beta production by microbial pathogens and their components.

Results/conclusions: To produce IL-1 beta, macrophages need a double stimulation with Toll like receptor (TLR) ligands that induce gene transcription, and NLR agonists (such as ATP or muramyl dipeptide (MDP)) that activate the inflammasome. Monocytes can release active IL-1 beta upon stimulation with TLR ligands alone. This probably represents an adaptation of each cell type to its environment.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Inflammation / physiopathology*
  • Interleukin-1beta / biosynthesis
  • Receptors, Cell Surface / physiology*
  • Toll-Like Receptors / physiology*

Substances

  • Interleukin-1beta
  • Receptors, Cell Surface
  • Toll-Like Receptors