Abstract:
:ME3738 is a new compound that attenuates liver disease in several models of acute and chronic liver inflammation. We used the concanavalin A (Con A) model to elucidate the molecular mechanisms of ME3738 to block liver cell damage. Pretreatment of BALB/c mice with ME3738 prior to Con A injection resulted in a significant reduction in liver injury. The protective effect of ME3738 prior to Con A injection was associated with a reduction in IL-6 serum levels and NF-kappaB DNA binding in liver nuclear extracts. However, STAT3 DNA binding was induced via ME3738 prior to Con A injection. Further analysis showed that ME3738 induces IL-6 serum levels and activates STAT3 DNA binding and target gene transcription. The relevance of this finding was assessed in IL-6(-/-) mice. In these animals, ME3738 induced no increase in IL-6 serum expression, and activation of IL-6-dependent pathways was not found. In addition, ME3738 did not protect IL-6(-/-) animals from Con A-induced liver failure, while IL-6 injection was still effective. Therefore, we demonstrate that ME3738 triggers IL-6 expression, which activates pathways that are relevant to protect from Con A-induced liver failure.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Klein C,Wüstefeld T,Heinrich PC,Streetz KL,Manns MP,Trautwein Cdoi
10.1002/eji.200323651keywords:
subject
Has Abstractpub_date
2003-08-01 00:00:00pages
2251-61issue
8eissn
0014-2980issn
1521-4141journal_volume
33pub_type
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