Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy.

BACKGROUND/AIMS: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is poorly understood.

OBJECTIVE

This study aimed to explore the possible effect of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-α in ICP.

METHODS

Serum levels of cytokines IL-18, IL-12 and TNF-α, bile acids and hepatic function parameters were measured. The expression of HDAC3 in the placenta was determined by immunohistochemistry (IHC), western blotting and RT-PCR.

RESULTS

IL-18, IL-12 and TNF-α serum levels were significantly higher in the severe ICP group than in the mild ICP group and the control group, and the difference between the mild ICP group and control group was not significant. HDAC3 protein expression was identified in the nucleus of the placental trophoblast by IHC. HDAC3 mRNA and protein expression were significantly lower in the ICP groups (mild ICP and severe ICP groups) than in the control groups, and no significant difference was found between the mild ICP and severe ICP groups.

CONCLUSIONS

The low expression of HDAC3 and overexpession of inflammatory cytokines (IL-18, IL-12 and TNF-α) in ICP may be involved in liver cell apoptosis. We suspect that HDAC3 may play an important role in the pathophysiology of ICP.