The mechanism of Toll-like receptor 4 pathway in lung injury induced by severe acute pancreatitis in mice

Abstract

Objective To investigate mechanism of Toll-like receptor 4 (TLR4) pathway in lung injury of severe acute pancreatitis (SAP). Methods The SAP model were induced in TLR4-/-and TLR4+ /+ mice and were randomly divided into group A: TLR4+ /+ group, B: TLR4+ /+ -SAP group, C: TLR4-/-group and D: TLR4-/--SAP group. The interleukins (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, IL-8 concentration of serum were detected by enzyme-linked immunoabsorbent assay; pathological changes of pancreas and lung were observed by hematoxylin-eosin; T helper cell 17 (Th17) and regulatory T cell (Treg) cells were detected by flow cytometry; mRNA expression of IL-17, forkhead box P3 (Foxp3), receptor-γt (RORγt) were detected by real-time polymerase chain reaction, p-signal transducer and activators of transcription (STAT)-3 and nuclear factor-κB (NF-κB) protein were detected by Western blotting. Results Compared with A and C group, serum IL-6, TNF-α, IL-1β and IL-8 concentrations were significantly increased in group B (P<0.05); Th17/Treg cells were significantly increased (P<0.05); levels of IL-17, Foxp3 and RORγt mRNA were significantly increased (P<0.05); expression of p-STAT-3 or NF-κB in B and D group were significantly higher than those in group A and group C. Compared with TLR4+ /+ -SAP group, concentration of cytokines in TLR4-/--SAP group was significantly lower than that of group (P<0.05) and levels of IL-17, Foxp3, RORγt, Th17 and Treg cells, levels of p-STAT-3 and NF-κB protein were significantly lower (P<0.01). Conclusion Blocking TLR4 pathway can reduce inflammation and lung injury in SAP. Key words: Severe acute pancreatitis; Toll-like receptor 4; T helper cell 17; Regulatory T cells; Inflammation