Corticotropin-releasing factor induces inflammatory cytokines via the NLRP6-inflammatory cytokine axis in a murine model of irritable bowel syndrome.

AIM: As a stress-related disorder, irritable bowel syndrome (IBS) has aberrant brain-gut communication and low-grade inflammation in the intestine. This study determined the effect of corticotropin-releasing factor (CRF) on regulating the NOD-like receptor pyrin domain-containing protein 6 (NLRP6)- inflammatory cytokine axis in a murine model of IBS.

METHODS: C57BL/6 mice were subjected to water avoidance stress (WAS) for 1 h/day over the course of 10 days. We assessed the abdominal withdrawal reflex (AWR) and colon inflammation histology in IBS mice. We also measured the levels of CRF, NLRP6 inflammasome components, myeloperoxidase (MPO), D-lactate (D-LA), interleukin-1β (IL-1β), and IL-18. We used the Caco2 cell line to confirm the in vivo data. In addition, we assessed the effect of Clostridium butyricum (C. butyricum) on IBS mice.

RESULTS: IBS mice exhibited visceral hypersensitivity and inflammation, accompanied by increases in CRF, MPO, D-LA, IL-1β, and IL-18, but a decrease in NLRP6 expression. Our in vitro data showed that CRF suppressed NLRP6, but induced IL-1β and IL-18 levels, in Caco2 cells. In addition, C. butyricum restored CRF levels and maintained the NLRP6-inflammatory cytokine axis in IBS mice.

CONCLUSIONS: CRF induces the NLRP6-inflammatory cytokine axis in IBS mice, and C. butyricum could be beneficial in controlling IBS.