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J Hepatol. 2005 Apr;42(4):548-56.

Interleukin-6 protects hepatocytes from CCl4-mediated necrosis and apoptosis in mice by reducing MMP-2 expression.

Author information

1
Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA. meena.bansal@mssm.edu

Abstract

BACKGROUND/AIMS:

Interleukin-6 stimulates liver regeneration and promotes hepatoprotection following experimental liver injury, but underlying mechanisms have not been fully characterized. Because studies suggest matrix metalloproteinase-2 (MMP-2) may promote liver injury, we examined whether IL-6 exerted its protective effects via regulation of MMP-2.

METHODS:

MMP-2 was analyzed in livers of IL-6-/- and IL-6+/+ mice following CCl(4) administration. IL-6-/- mice were pretreated with IL-6 and liver histology and MMP-2 expression were examined after liver injury. IL-6-/- mice were treated with an MMP-2 inhibitor and assessment of injury (histology and serum ALT levels), apoptosis by TUNEL assay, and hepatocyte proliferation by BRDU-labeling was performed. These studies were complemented by analysis of cultured stellate cells.

RESULTS:

MMP-2 mRNA, protein, and activity was increased in IL-6-/- livers. Restoration of IL-6 signaling in IL-6-/- mice rescued injury and restored MMP-2 expression to wild-type levels. Furthermore, pharmacologic inhibition of MMP-2 decreased hepatocellular injury and apoptosis in IL-6-/- mice. In cultured stellate cells, recombinant IL-6 suppressed endogenous MMP-2 mRNA and protein expression.

CONCLUSIONS:

IL-6 may be hepatoprotective in acute injury through down-regulation of MMP-2. These findings suggest a role for MMP-2 in amplifying liver injury in vivo.

PMID:
15763341
PMCID:
PMC2893541
DOI:
10.1016/j.jhep.2004.11.043
[Indexed for MEDLINE]
Free PMC Article

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