TcdA/B-induced intestinal inflammation and permeability are attenuated by inhibiting the P2y₆ receptor <i>in</i><i>vivo</i>.

<p>(A) Intrarectal instillation of TcdA/B (50 μg/100 μL for 4 hrs) triggers a significant increase in colonic tissue myeloperoxidase (MPO), an effect that is significantly reduced by pretreating mice with the P2Y₆ inhibitor MRS 2578 (100 μL of 10 μM; in PBS via intrarectal instillation). N = 6/group; * denotes p<0.05 compared to PBS vehicle groups; # denotes p<0.05 compared to TcdA/B treatment with vehicle (DMSO). (B) Pretreating mice with MRS 2578 (100 μL of 10 μM; in PBS via intrarectal instillation) inhibits TcdA/B-induced increases in permeability as assessed by FITC-flux from the colonic lumen in to the serum. N = 6/group; * denotes p<0.05 compared to PBS vehicle groups; # denotes p<0.05 compared to TcdA/B treatment with vehicle (DMSO). (C) Pretreating mice with MRS 2578 reduces the histological inflammatory score and the (D) percentage of the colonic tissue section exhibiting architectural changes (% architecture change). N = 12 sections/group; * denotes P<0.05 compared to vehicle pretreatment. (E) Representative colonic sections stained with hematoxylin and eosin from mice treated with vehicle, MRS2578 alone, vehicle + TcdA/B and MRS2578 + TcdA/B; N = 6/group.