Inhibition of Toll-like receptor 4 with vasoactive intestinal peptide attenuates liver ischemia-reperfusion injury

Toll-like receptor 4 (TLR4) has attracted a great deal of attention in ischemia-reperfusion (IR) injury in recent years. Vasoactive intestinal peptide (VIP) plays an important role in anti-inflammatory and immunomodulatory activity in several animal models. There are no data available regarding the effect of VIP on TLR4 expression in IR injury in vivo. In the present study, we study the effect of VIP on TLR4 expression in mouse macrophage cell line RAW 264.7 and a mouse partial IR model.

The potential inhibitory effect of VIP on TLR4 mRNA and protein in a mouse macrophage cell line and in a mouse model of partial warm hepatic IR injury was assessed. We also assessed the expression tumor necrosis factor (TNF)-α and interleukin (IL)-6 in this model.

Expression of TLR4 mRNA levels was significantly decreased at 6, 12, and 24 hours after treat with VIP in mouse macrophage cell line RAW 264.7. Expression of TLR4 mRNA, TLR4 protein, alanine aminotransferase, TNF-α, and IL-6 levels were significantly increased in the IR group but significantly decreased in groups pretreated with VIP at a concentration of 5 and 10 nmol. Hematoxylin and eosin staining show apparent edema and necrosis were observed in the IR group, but in the VIP pretreatment group, edema and necrosis in IR modes were reduced.

This study showed that VIP might inhibit TLR4 in vitro and in vivo, and pretreatment with VIP might inhibited TLR4 activation and reduced warm IR injury.