Understanding the regulation of pattern recognition receptors in inflammatory diseases - a 'Nod' in the right direction

Abstract

Nucleotide-binding oligomerization domain (NOD) -like receptors (NLRs) are a family of 23 receptors known as pattern recognition receptors; they are expressed in many cell types and play a key role in the innate immune response. The NLRs are activated by pathogen-associated molecular patterns, which include structurally conserved molecules present on the surfaces of bacteria. The activation of these NLRs by pathogens results in the downstream activation of signalling kinases and transcription factors, culminating in the transcription of genes coding for pro-inflammatory factors. Expression of NLR is altered in many cellular, physiological and disease states. There is a lack of understanding of the mechanisms by which NLR expression is regulated, particularly in chronic inflammatory states. Genetic polymorphisms and protein interactions are included in such mechanisms. This review seeks to examine the current knowledge regarding the regulation of this family of receptors and their signalling pathways as well as how their expression changes in disease states with particular focus on NOD1 and NOD2 in inflammatory bowel diseases among others.

Keywords: NLR expression; NOD1; NOD2; inflammation; inflammatory bowel disease.

Figure 1

Nucleotide‐binding oligomerization domain (NOD)‐like receptor (NLR) pro‐inflammatory signalling pathway. The biochemical pathways shown in this figure pertain to NOD1 and NOD2 receptors that have been activated by γ‐d‐glutamyl‐mesodiaminopimelic acid or muramyl dipeptide.