Components of the mitogen-activated protein kinase cascade are activated in hepatic cells by Echinococcus multilocularis metacestode

AIM: To explore the effect of Echinococcus multilocularis on the activation of mitogen-activated protein kinase (MAPK) signaling pathways and on liver cell proliferation, METHODS: Changes in the phosphorylation of MAPKs and proliferating cell nuclear antigen (PCNA) expression were measured in the liver of patients with alveolar echinococcosis (AE). MAPKs, MEK1/2 [MAPK/extracellular signal-regulated protein kinase (ERK) kinase] and ribosomal S6 kinase (RSK) phosphorylation were detected in primary cultures of rat hepatocytes in contact in vitro with (1) E multilocularis vesicle fluid (EmF), (2) E multilocularis-conditioned medium (EmCM). RESULTS: In the liver of AE patients, ERK 1/2 and p38 MAPK were activated and PCNA expression was increased, especially in the vicinity of the metacestode. Upon exposure to EmF, p38, c-Jun N-terminal kinase (JNK) and ERK1/2 were also activated in hepatocytes in vitro, as well as MEK1/2 and RSK, in the absence of any toxic effect. Upon exposure to EmCM, only JNK was up-regulated. CONCLUSION: Previous studies have demonstrated an influence of the host on the MAPK cascade in E. multiloculal-is. Our data suggest that the reverse, i.e. para site-derived signals efficiently acting on MAN signaling pathways in host liver cells, is actually operating. (C) 2009 The WJG Press and Baishideng. All rights reserved.