Statins can be the potential therapeutic agents for reducing infection evoked cholangiopathy after liver transplantation?
Biliary infection, including bacteria and cytomegalovirus (CMV), can induce inflammatory response and lead to bile duct damage after liver transplantation. This process may involve a major class of pattern recognition receptors-TLRs (Toll-like receptors). Stimulation of these receptors by pathogens (CMV, bacteria, etc.) in bile duct can induce the secretion of a series of cytokines/chemokines mainly via a TLR-2/4-MyD88-dependent pathway. Strategies for prevention and treatment of biliary infection, such as selective digestive decontamination (SDD) and preemptive therapy with gancyclovir and antibiotics are not so satisfactory. Statin, a HMG-CoA reductase inhibitor, have special anti-inflammatory abilities. They can inhibit the expression of TLR-4 and TLR-2, and block the signaling pathways of LPS (TLR-2/4), virus-encoded envelope proteins (TLR-2) and HSP70 (TLR-2/4), This process can lead to a reduction of effector cytokines/chemokines. In addition, statins can suppress the replication of CMV by reducing NF-kappaB binding activity. We hypothesized that statins can be useful for reducing infection evoked cholangiopathy after liver transplantation. We provide reliable evidence supporting the hypothesis and offer proposals for future application.
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, PR China.
Jian
J
Wu
Pengfei
P
Yu
Zhenhua
Z
Hu
Shusen
S
Zheng
D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D002761:Cholangitis / Q000209:etiology* / Q000517:prevention & control*; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051193:Toll-Like Receptors