Inflammasomes are differentially expressed in cardiovascular and other tissues

Int J Immunopathol Pharmacol. Apr-Jun 2009;22(2):311-22. doi: 10.1177/039463200902200208.

Abstract

To determine the expression of components in Toll-like receptors (TLRs)/Nod-like receptors (NLRs)/inflammasome/caspase-1/interleukin (IL-1)-beta pathway, we examined the expression profiles of those genes by analyzing the data from expression sequence tag cDNA cloning and sequencing. We made several important findings: firstly, among 11 tissues examined, vascular tissues and heart express fewer types of TLRs and NLRs than immune and defense tissues including blood, lymph nodes, thymus and trachea; secondly, brain, lymph nodes and thymus do not express proinflammatory cytokines IL-1beta and IL-18 constitutively, suggesting that these two cytokines need to be upregulated in the tissues; and thirdly, based on the expression data of three characterized inflammasomes (NALP1, NALP3 and IPAF inflammasome), the examined tissues can be classified into three tiers: the first tier tissues including brain, placenta, blood and thymus express inflammasome(s) in constitutive status; the second tier tissues have inflammasome(s) in nearly-ready expression status (with the requirement of upregulation of one component); the third tier tissues, like heart and bone marrow, require upregulation of at least two components in order to assemble functional inflammasomes. Our original model of three-tier expression of inflammasomes would suggest a new concept of tissue inflammation privilege, and provides an insight to the differences among tissues in initiating acute inflammation in response to stimuli.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Apoptosis Regulatory Proteins / genetics
  • CARD Signaling Adaptor Proteins / genetics
  • Calcium-Binding Proteins / genetics
  • Cardiovascular System / immunology*
  • Carrier Proteins / genetics
  • Cells, Cultured
  • Endothelial Cells / immunology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Inflammation / genetics*
  • Inflammation / immunology
  • Interleukin-18 / genetics
  • Interleukin-1beta / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nod Signaling Adaptor Proteins / genetics
  • Signal Transduction / genetics*
  • Signal Transduction / immunology
  • Toll-Like Receptors / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRC4 protein, human
  • NLRP1 protein, human
  • NLRP3 protein, human
  • Nod Signaling Adaptor Proteins
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha