Figure 3

PD-L1 deficiency reduces the sepsis-induced increase in tissue cytokine levels and intestinal permeability while restoring intestinal TJ protein expression following CLP. C57BL/6 and PD-L1 deficient (−/−) mice were subjected to sham or CLP. Twenty-four hours later, the small intestine tissues were harvested for cytokine and TJ protein analysis. (A) Tissue levels of TNF-α, MCP-1 and IL-6 (pg/mL) are increased in septic C57BL/6 mice compared with the shams. However, these cytokine/chemokine levels are significantly decreased in PD-L1−/− CLP mice compared with septic C57BL/6 mice. IL-10 levels are not changed in all groups. (B) The extent of expression of TJ proteins claudin-1, occludin and ZO-1 in the ileum is significantly reduced in septic C57BL/6 mice compared with shams. PD-L1 gene deficiency prevents the decline of these proteins following CLP. (C) Intestinal permeability, as an index of intestinal dysfunction, was assessed by a ligated loop model in vivo. Following sepsis, there is a significant increase in the passage of fluorescein isothiocyanate-conjugated dextran (FD4) from the intestinal lumen to the circulatory system in C57BL/6 mice, while PD-L1 gene deficiency markedly reduces sepsis-induced intestinal permeability. * P < 0.05 versus sham mice; # P < 0.05 versus PD-L1−/− CLP mice. One-way ANOVA and Student-Newman-Keuls test; mean ± SEM; n = 6–8 mice/group.