Casein phosphopeptide SIER1P attenuates dextran sodium sulfate-induced inflammatory injury in intestinal organoid 2-dimensional monolayer cultures by inhibiting the calcium-sensing receptor/NF-κB signaling pathway

Abstract

This study was aimed to explore the mechanism of casein phosphopeptide SIER1P affecting intestinal mucosal barrier function based on calcium-sensing receptor (CaSR)/NF-κB signaling pathway. Porcine intestinal organoid-derived 2-dimensional (2D) monolayer cultures were used and randomly assigned in this study. SIER1P obtained by hydrolysis of α_s1-CN improved the damage of intestinal organoid 2D monolayer intestinal epithelial barrier by dextran sulfate sodium (DSS). Five micrograms/milliliter SIER1P could significantly alleviate the increased expression levels of inflammatory factors, and the decreased expression levels of tight junction proteins occludin, claudin-1, and ZO-1 induced by DSS. Simultaneously, SIER1P significantly alleviated the DSS-induced expression levels increasing of CaSR in organoid-derived 2D monolayer cultures. Spermine (CaSR activator) attenuated the roles of SIER1P on ameliorating the secretion level of inflammatory cytokines and the expression level of tight junction proteins. The CaSR inhibitor NPS2143 showed a tendency to further promote the effects of SIER1P on ameliorating the expression levels of inflammatory factors and tight junction proteins. SIER1P also alleviated the DSS-induced expression levels increasing of PI3K, PLC, and pNF-κB. These results suggest that casein phosphopeptide SIER1P has a protective effect on DSS-induced inflammatory injury in intestinal organoid-derived 2D monolayer cultures through 2 signaling pathways, CaSR/PI3K/NF-κB and CaSR/PLC/NF-κB.