The HCV/CyA/MMF

combination reduced cell viability by 2.8-fold, and increased clCas3 and clPARP by 18.3- and 32.7-fold respectively. A similar effect was seen with the combination of HCV/Tac/MMF and HCV/Sir/MMF. In HCV-infected PMoH exposed to either CyA, Tac or Sir, caspase inhibition with Q-VD improved cell viability RXDX-106 by 58%, 53%, and 43%, reduced clCas3 by 88%, 89%, and 83%, and reduced clPARP by 93%, 92%, and 92% respectively. These significant improvements with Q-VD were also seen in HCV-infected cells exposed to CyA or Tac or Sir + MMF. Conclusion: In HCV-infected hepatocytes, CyA, Tac and Sir were all found to increase hepatocyte apoptosis. These findings help explain the accelerated progression of liver disease in post-transplant HCV recurrence. The finding that Q-VD reversed hepatocyte cell death in this setting provides

a rationale for targeting apoptosis to reduce liver injury here. F HACZEYNI,1 A MRIDHA,1 M YEH,2 N TEOH,1 G FARRELL1 1Liver Research Group, ANU Medical School, The Canberra Hospital, ACT. 2Department of Pathology, University of Washington, Seattle, WA, USA Introduction/Aims: In unhealthy obesity, adipose inflammation is associated with STI571 price insulin resistance and non-alcoholic steatohepatitis (NASH). However, the mechanism of adipose inflammatory recruitment is unknown. We studied whether Toll-like receptor 9 (Tlr9) and intracellular adapter protein Myeloid differentiation factor (MyD) 88 (signalling intermediate of multiple TLRs) play a role in adipose inflammation and development of NASH. Methods: Female Tlr9-/-, MyD88-/-, and wildtype (WT) mice (n = 6 − 14) on C57BL/6J (B6) strain were fed either rodent chow or atherogenic

(Ath) (SF03-020; Glen Forrest) diet from weaning to 24 weeks of age. Fasting blood, liver, and periovarian white adipose tissue (Pov WAT) and other fat pads were removed under anaesthesia for tissue and molecular analyses. Results: Ath diet increased body weight in all groups of mice, but deletion of Tlr9 reduced weight gain (32 g ± 0.9 Tlr9-/- vs. 43 g ± 1.8 WT p < 0.05). Similarly, Pov WAT weight expansion was less in Ath-fed Tlr9-/- than corresponding WT and MyD88-/- mice. Conversely, learn more liver weights increased in Ath-fed WT mice but significantly less in both Ath-fed Tlr9-/- and MyD88-/- counterparts. While grade 2–3 steatosis occurred in all Ath-fed mice, necroinflammatory score (Fig A) and NAFLD activity score (NAS) were less in Tlr9 and MyD88 deleted mice. Surprisingly, serum ALT levels were higher in Tlr9-/- and MyD88-/- than WT mice, even in those fed chow (p < 0.05) (Fig B). Further, ser insulin was higher in Ath-fed MyD88-/- mice than other groups, albeit fasting blood glucose levels were similar in all groups. In Pov WAT, adiponectin mRNA levels decreased with Ath dietary feeding in all groups compared to chow.