Regulation and Sensing of Inflammasomes and Their Impact on Intestinal Health

Abstract

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and hematopoitic interferon-inducible nuclear protein (HIN) domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated, some of these receptors oligomerize to form the structural backbone of a signalling platform known as an inflammasome. Inflammasomes promote the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. The gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome-deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population-based human studies. In this review, we summarise the most recent findings with regard to the formation, sensing, and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

Keywords: Crohn’s disease; IL-18; inflammasomes; interleukin (IL)-1β; ulcerative colitis.

Figure 1

Structure of the human nucleotide-binding oligomerization domain (NOD)-like receptor subgroups.

Figure 2

Formation of a NOD-like receptor protein inflammasome containing an N-terminal Pyrin domain.

Figure 3

The mechanism for the inflammasome-mediated, catalytic conversion of procaspase-1 to caspase-1.

Figure 4

Structure of the human pyrin and hematopoitic interferon-inducible nuclear protein (HIN) domain (PYHIN) family.