N (Fig. 2b; 30 minutes: 2 versus 4 mol/L, P 0.031; six hours: three versus 6 mol/L, P 0.017; 24 hours: 2.5 versus 5 mol/L, P 0.012).Intragraft Expression of Egr-1, ET-1, ETA, TNF- , MIP-2, and iNOS: Down-Regulation of Egr-1 PathwayThe intragraft mRNA levels of Egr-1 were considerably down-regulated at 30 minutes and six hours just after reperfusion in the FK group (Fig. 3a; 30 minutes: 77 versus 389 relative to basal level, P 0.034; six hours: 15 versus 258 relative to basal level, P 0.034). The intragraft protein levels of Egr-1 have been constant with the mRNA levels (Fig. 4). As for ET-1 and ETA, the intragraft mRNA levels were decreased significantly at two hours, six hours, and 24 hours immediately after liver ADAM10 Inhibitor Storage & Stability transplantation (Fig. 3b, 3c; ET-1, 2 hours: 33.5 versus 573 relative to basal level, P 0.034; 6 hours: 23 versus 392 relative to basal level, P 0.034; ETA, six hours: 157.5 versus 266 relative to basal level, P 0.021;hours: 151 versus 356 relative to basal level, P 0.021). Even though over-expression of intracellular ET-1 was discovered in both groups at 30 minutes after reperfusion (Fig. 5a-1, 5a-3), it decreased considerably at 24 hours immediately after reperfusion inside the FK group (Fig. 5a-2, 5a-4). The intragraft mRNA levels of TNF- had been downregulated within the FK group at six hours and 24 hours following liver transplantation compared with all the control group (Fig. 3d; six hours: 218 versus 682 relative to basal level, P 0.038; 24 hours: 115.5 versus 609.six relative to basal level, P 0.02). Both the intragraft mRNA level (Fig. 3e, 24 hours: 113.5 versus 672.5 relative to basal level, P 0.04) and protein degree of MIP-2 (Fig. 4) had been down-regulated right after FK 409 therapy. The intracellular protein expression of iNOS was substantially down-regulated at 24 hours soon after liver transplantation immediately after FK 409 treatment (Fig. 5b-2, 5b-4) compared using the manage group, though the comparable levels with the 2 groups were identified at 30 minutes immediately after reperfusion (Fig. 5b-1, 5b-3).Intragraft Expression of HO-1, A20, Hsp-70, Interferon- -Inducible Protein-10 (IP-10), CXCR2, CXCR3, and IL-10: Prior Induction of Hsps and Anti-inflammatory GenesBoth the intragraft mRNA (Fig. 6a, 6b) and protein expressions (Figs. 4 and 7) of HO-1 and A20 had been up2004 Lippincott Williams WilkinsAnnals of Surgery Volume 240, Quantity 1, JulyFK409 PKCθ list Attenuates Small Liver Graft InjuryFIGURE 7. Intracellular protein expression of (a) heme oxygenase-1 (HO-1) and (b) A20 in FK group at (1) 30 minutes and (two) 24 hours right after reperfusion, and that in control group at (3) 30 minutes and (4) 24 hours right after reperfusion. (HO-1: 400, A20: 200).FIGURE 8. Intracellular protein expression of (a) CXCR2 and (b) interleukin-10 (IL-10) in FK group at (1) 6 hours and (2) 24 hours immediately after reperfusion, and that in control group at (3) six hours and (4) 24 hours right after reperfusion. The sinusoidal dilation (arrow) was found at six hours following reperfusion in handle group (a-3). ( 200).regulated immediately after FK 409 therapy during the 1st 24 hours right after reperfusion. The peak from the mRNA degree of HO-1 inside the FK group reached 5393 relative to basal level at 6 hours right after reperfusion compared with the control group (781 relative to basal level, P 0.034) (Fig. 6a). The intragraft protein expression of HO-1 inside the FK group was located at its highest level at 24 hours after reperfusion by Western blot (Fig. four). The intracellular protein expression by immunostaining demonstrated that over-expression of HO-1 was mostly identified in sinusoidal endothelial cel.
