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

Objective This study aimed to determine 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 irritable bowel syndrome (IBS). Methods C57BL/6 mice were subjected to water avoidance stress (WAS) for 1 h per day for 10 days, and the abdominal withdrawal reflex (AWR) and colonic inflammation were assessed. We also measured the levels of CRF, NLRP6 inflammasome components, myeloperoxidase, D-lactate, interleukin (IL)-1 beta, and IL-18. In vitro experiments with Caco-2 cell line were also performed. 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, myeloperoxidase, D-lactate, IL-1 beta, and IL-18 levels, but a decrease in NLRP6 expression. In vitro data showed that CRF suppressed NLRP6, but induced IL-1 beta and IL-18 levels, in Caco-2 cells. 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. C. butyricum could be beneficial in controlling IBS.