Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that includes ulcerative colitis (UC) and Crohn’s disease (CD). with colitis-associated colorectal cancer (CAC) being a progressive intestinal inflammation due to inflammatory bowel disease (IBD). While this is an exemplification of the negatives of inflammation, it is just as crucial to have some degree of the inflammatory process to maintain a healthy immune system. A pivotal component in the maintenance of such intestinal homeostasis is the innate immunity component, inflammasomes. Inflammasomes are large, cytosolic protein complexes formed following stimulation of microbial and stress signals that lead to the expression of pro-inflammatory cytokines. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been extensively studied in part due to its strong association with colitis and CAC. The aryl hydrocarbon receptor (AhR) has recently been acknowledged for its connection to the immune system aside from its role as an environmental sensor. AhR has been described to play a role in the inhibition of the NLRP3 inflammasome activation pathway.
The NLRP3 inflammasome is one of the most extensively studied NLRs due to its clinical relevance in a wide range of human diseases. This 115 kDa cytosolic protein complex consists of a triadic constitution; the NACHT scaffold which serves as a central oligomerization domain with an ATPase activity, the N-terminal PYCARD adaptor which recruits the apoptosis-associated speck-like protein (ASC) and the C-terminal leucine-rich repeat (LRR) which are thought to be involved in detecting stimuli [11,14].
Pathways | Mechanism | Ref. |
---|---|---|
AhR/STAT1–NF-κB axis | Quaking inhibits NF-κB transcriptional activity and prevents NLRP3 inflammation via AhR-dependent manner | [153] |
NAD+/SIRT1/SUV39H1/H3K9me3 axis | Ameliorates colitis through promotion of Treg differentiation | [170] |
LncRNA-PVT1-STAT3 axis | Inhibits STAT3 via LncRNA-PVT1 from promoting signals for cancer inflammation | [173] |
AhR/Nrf2/NQO1 axis | AhR up-regulates Nrf2 and NQO1 levels in the colon and prevents NLRP3 inflammasome activation | [175] |
Fibronectin/integrin β1/FAK axis | Promotes cancer metastasis through ANRT down-regulation | [180] |
This entry is adapted from the peer-reviewed paper 10.3390/molecules25102427