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World J Gastroenterol. May 7, 2009; 15(17): 2116-2124
Published online May 7, 2009. doi: 10.3748/wjg.15.2116
Components of the mitogen-activated protein kinase cascade are activated in hepatic cells by Echinococcus multilocularis metacestode
Ren-Yong Lin, Jun-Hua Wang, Xiao-Mei Lu, Xiao-Tao Zhou, Georges Mantion, Hao Wen, Dominique A Vuitton, Lysiane Richert
Ren-Yong Lin, Jun-Hua Wang, Xiao-Mei Lu, Xiao-Tao Zhou, Hao Wen, Xinjiang Key Laboratory on Echinococcosis and Liver Surgery, 1st Teaching Hospital of Xinjiang Medical University, No.1 Liyushan Road, Urumqi 830054, China
Ren-Yong Lin, Lysiane Richert, Laboratoire de Toxicologie Cellulaire, EA 4267, Faculté de Médecine et Pharmacie, University of Franche-Comté, Place Saint-Jacques, 25030 Besançon, France
Georges Mantion, Liver Surgery and Transplantation Unit, EA 3921, Department of Digestive Surgery, University Hospital Jean Minjoz, Boulevard Fleming, 25030 Besançon, France; WHO-Collaborating Centre for the Prevention and Treatment of Human Echinococcosis, University of Franche-Comté, Place Saint Jacques, 25030 Besançon, France
Dominique A Vuitton, WHO-Collaborating Centre for the Prevention and Treatment of Human Echinococcosis, University of Franche-Comté, Place Saint Jacques, 25030 Besançon, France
Author contributions: Lin RY originated the study, he performed most of the experimental work, analyzed the data and prepared the figures and the draft versions of the manuscript; Wang JH and Lu XM were involved in the collection, preservation and pathological identification of the human liver samples in Urumqi, China; Zhou XT contributed to the immunostainings and measurements performed on these samples; Mantion G and Wen H, hepatic surgeons, contributed to the design of the study, to the diagnosis, surgical treatment and follow-up of the patients with alveolar echinococcosis and supervised in vivo studies; Vuitton DA contributed to the design of the study, and interpretation of the data; Richert L was much involved in the interpretation of the data and revised all draft versions and the definitive version of the manuscript.
Correspondence to: Lysiane Richert, Professor, Laboratoire de Toxicologie Cellulaire, EA 4267, Faculté de Médecine et Pharmacie, University of Franche-Comté, Place Saint-Jacques, 25030 Besançon, France. lysiane.richert@yahoo.com
Telephone: +33-3-81665553
Fax: +33-3-81665679
Received: January 10, 2009
Revised: March 19, 2009
Accepted: March 26, 2009
Published online: May 7, 2009
AIM: To explore the effect of Echinococcus multilocularis (E. 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. multilocularis. Our data suggest that the reverse, i.e. parasite-derived signals efficiently acting on MAPK signaling pathways in host liver cells, is actually operating.
