Curcumin inhibits NF-kappaB activation and reduces the severity of experimental steatohepatitis in mice.
OBJECTIVE
While oxidative stress is a feature of non-alcoholic steatohepatitis, the causal link between oxidative stress and inflammatory recruitment has yet to be demonstrated. We analysed the role of NF-kappaB redox-sensitive signalling pathway of inflammatory recruitment in experimental steatohepatitis.


METHODS
Mice were fed the methionine and choline deficient (MCD) or the control diet, with or without curcumin, an NF-kappaB inhibitor, for up to 4 weeks. Histopathology, lipoperoxides, NF-kappaB/DNA binding and expression of NF-kappaB-regulated genes were assessed.


RESULTS
MCD-fed mice developed steatohepatitis accompanied by dramatic accumulation of hepatic lipoperoxides, activation of NF-kappaB and induction of pro-inflammatory ICAM-1, COX-2, MCP-1 and CINC mRNA. Curcumin significantly reduced MCD-induced inflammation but had no effect on steatosis or on the level of hepatic lipid peroxides. Curcumin prevented the MCD-induced activation of NF-kappaB and decreased downstream induction of ICAM-1, COX-2 and MCP-1. However, it failed to reduce activation of AP-1, MAPK pathways or CINC expression.


CONCLUSIONS
Curcumin alleviates the severity of hepatic inflammation in experimental steatohepatitis induced by the MCD diet, an effect likely to be mediated via inhibition of NF-kB activation and dependent pro-inflammatory genes. The NF-kappaB pathway is one among several possible signalling pathways by which inflammation is recruited in experimental steatohepatitis.
Leclercq
Isabelle A
IA
Gastroenterology Unit, Université Catholique de Louvain (UCL), GAEN/UCL 53/79, Avenue E. Mounier, 53, B-1200 Brussels, Belgium. isabelle_leclercq@wmi.usyd.edu.au
Farrell
Geoffrey C
GC
Sempoux
Christine
C
dela Peña
Aileen
A
Horsmans
Yves
Y
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D002796:Choline Deficiency / Q000150:complications; D024042:Collagen Type I / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D003677:Deficiency Diseases / Q000150:complications; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008715:Methionine / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index; D018808:Transcription Factor AP-1 / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024042:Collagen Type I; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D008715:Methionine; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin