Inhibition of PI3K/AKT and JNK attenuated
the induction of IL-23 by TCA; whereas, p38 inhibition enhanced TCA-induced IL-23 production. Overall, these studies identified the key signal transduction www.selleckchem.com/products/r428.html pathways that mediate the interaction between bile acids and the IL-23/IL-17A axis. Pharmacological targeting of these pathways could alleviate hepatic inflammation and injury in patients with cholestatic liver disease. Disclosures: The following people have nothing to disclose: Kate M. O’Brien, Kara Kelly, Bryan Copple Introduction: It is unclear whether liver injury in acute hepatitis E is due to virus-induced cytolysis or the host immune response. We therefore studied host gene expression and enumerated immune cells in liver tissues from fulminant hepatitis E (FHF-E) patients, in comparison with healthy livers and those from fulminant hepatitis B (FHF-B) patients. Methods: Microarray-based expression profiling was done on post-mortem liver tissue http://www.selleckchem.com/products/SP600125.html from 5 FHF-E and 6 FHF-B patients, and normal liver tissue from 6 persons. Differential expression was defined as ≥2.0-fold change with Benjamini-Hochberg corrected p-value below 0.05. CD4+, CD8+ and CD56+ cells were counted using immunohistochemistry.
Results: Compared to normal, the livers from FHF-E and FHF-B showed differential expression of 3377 (up-regulated 1703, down-regulated 1674) and 2572 (up 1164, down 1408) entities, respectively. This included 2142 (up 896, down 1246) entities that were common between the two sets; most of these belonged to metabolic, hemostatic (intrinsic and extrinsic prothrombin activation), and complement (classical, alternative and lectin-induced) pathways. Analysis of 1235 (up 807, down 428) entities with differential expression in FHF-E but not in FHF-B showed activation of several immune response pathways, particularly those involving cytotoxic T cells (Table). CD8+ T cells were increased in both FHF-E (median 53.4 [range 31.2-99.9]) and FHF-B (49.3 [19.3-51]; p=0.005) compared to controls (6.9 [3.1-14.9]). Conclusion: Liver tissue from FHF-E patients
showed increased expression of genes belonging to cytotoxic T cell effector pathways, accompanied by CD8+ T cell 上海皓元 infiltration. This suggests a role for CD8+ T cells in the pathogenesis of hepatitis E. Pathways whose genes were over-represented among entities differentially expressed in fulminant hepatitis E (FHF-E), and in FHF-E but not in fulminant hepatitis B (FHF-B) Disclosures: The following people have nothing to disclose: Anshu Naik, Amit Goel, Vinita Agrawal, Aditya N. Sarangi, Nanda Chhavi, Vineeta Singh, Shahid Jameel, Rakesh Aggarwal 501 CEACAM1 (Carcinoembryonic antigen-related cell adhesion molecule 1) protects from acute immune-mediated liver injury The T cell mitogenic plant lectin concanavalin A (ConA) induces acute immune-mediated liver injury. Hallmarks of liver injury are increased plasma transaminase activities and the release of pro-inflammatory cytokines.