Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A

Citation
K. Kimura et al., Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A, INT IMMUNOL, 11(9), 1999, pp. 1491-1500
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOLOGY
ISSN journal
0953-8178 → ACNP
Volume
11
Issue
9
Year of publication
1999
Pages
1491 - 1500
Database
ISI
SICI code
0953-8178(199909)11:9<1491:IOHFIC>2.0.ZU;2-Z
Abstract
Liver fibrosis is commonly observed in chronic liver disease, However, the immunological mechanisms underlying hepatic fibrosis due to chronic inflamm ation are not well defined, mainly because suitable experimental models hav e not been established, We have found that weekly i.v. administration of co ncanavalin A (Con A) in BALB/c mice brought about a striking alanine aminot ransferase increase, resulting in piecemeal necrosis with bridging fibrosis in the parenchyma, Using this fibrosis model, we demonstrated the kinetics of cytokine mRNA expression in liver, Transforming growth factor (TGF)-bet a 1, TGF-alpha, basic fibroblast growth factor (bFGF) and hepatocyte growth factor mRNAs were up-regulated after each Con A administration. Furthermor e, either anti-IFN-gamma, anti-tumor necrosis factor (TNF)-alpha or anti-TG F-beta mAb given together with Con A markedly inhibited the development of hepatic fibrosis, Treatment with either anti-IFN-gamma or anti-TNF-alpha mA b also completely prevented hepatic injury; in contrast, treatment with ant i-TGF-beta mAb did not. The treatment with anti-TGF-beta mAb did not affect the levels of hepatic mRNAs for either IFN-gamma or TNF-alpha after Con A injection. Treatment with either anti-IFN-gamma or anti-TNF-alpha did not a ffect the expression levels of TGF-beta in the liver, In conclusion, the co ntinuous presence of both severe liver damage and up-regulation of TGF-beta synthesis is necessary to induce hepatic fibrosis in this model.