Synthetic phosphoserine dimer attenuates lipopolysaccharide‐induced inflammatory response in human intestinal epithelial cells via activation of NF‐κB and MAPKs cell signalling pathways

Abstract

SummaryPrevious studies have shown that phosvitin phosphopeptides could exert anti‐inflammatory activity in lipopolysaccharide (LPS)‐stimulated small intestine epithelial cells. However, the role of phosphopeptides in inflammation‐related cell signalling pathways remains to be elucidated. Here, the anti‐inflammation effect of a synthetic phosphoserine dimer (2PS) in cell signalling pathways were evaluated by PCR array and immunoblotting assays. Our results showed that 2PS led to reduced secretion of LPS‐induced IL‐8 in a dose‐dependent manner, and downregulation of the mRNA expression of pro‐inflammation cytokines in HT‐29 cell cultures, including IL‐8, IL‐6, IL‐12, TNF‐α and MCP‐1. Compared to LPS alone, treatment with 2PS + LPS exerted downregulation of gene expression in the TLR4‐related cell signalling pathway, including MyD88, IRAK1, IKKε and IKKγ, as well as transcription factors RELs, JUN, and FOS. At the protein level, cell treatment with 2PS led to a decline in LPS‐induced phosphorylation of IκB, ERK1/2, and p‐38 MAPKs. Our results indicate that 2PS attenuates LPS‐induced inflammation through down‐regulation of NF‐κB pathway and inhibition of MAPKs phosphorylation.