Toll-Like Receptor 9 Signaling Pathway Contributes to Intestinal Mucosal Barrier Injury in Mice With Severe Acute Pancreatitis

Objectives: The purpose of this study was to investigate the role and mechanism of toll-like receptor 9 (TLR9) in intestinal mucosal barrier injury in mice with severe acute pancreatitis (SAP). Methods: The mice were randomly divided into 3 groups: control group, SAP group, and TLR9 antagonist-treated group. The expression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, diamine oxidase, and endotoxin core antibodies were detected by enzyme-linked immunosorbent assay. The protein expression of zonula occluden-1 (ZO)-1, occludin, TLR9, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), p-nuclear factor (NF)-kappa B p65, and NF-kappa B p65 were detected by Western blot. TdT-mediated dUTP nick-end labeling staining was used for detecting intestinal epithelial cell apoptosis. Results: The expression of TLR9 and its related pathway proteins MyD88, TRAF6, and p-NF-kappa B p65 in the intestinal tract of SAP mice were significantly increased compared with that of control mice. Inhibition of the TLR9 expression could reduce the level of serum proinflammatory cytokines, reduce the apoptosis of intestinal epithelial cells, improve intestinal permeability, and ultimately reduce the damage of intestinal mucosal barrier function in SAP. Conclusions: Toll-like receptor 9/MyD88/TRAF6/NF-kappa B signaling pathway plays an important role in intestinalmucosal barrier injury of SAP.

Automated summary

This study investigated the role and mechanism of Toll-like receptor 9 (TLR9) in intestinal mucosal barrier injury in mice with severe acute pancreatitis (SAP). The results showed that the TLR9/MyD88/TRAF6/NF-kappa B signaling pathway plays an important role in the damage of intestinal mucosal barrier function in SAP. Inhibition of TLR9 expression could reduce inflammation, apoptosis of intestinal epithelial cells, and improve intestinal permeability.