4-Hydroxynonenal decreases interleukin-6 expression and protein production in primary rat Kupffer cells by inhibiting nuclear factor-B activation

Kupffer cells have been documented to play an important role in the early events of liver injury and regeneration by releasing biologically active mediators such as interleukin-6 (IL-6). 4-Hy-droxy-trans-2-nonenal (4-HNE), a major end product of lipid peroxidation, has multiple cytotoxic effects and is implicated in chemical-induced liver injury. Consequently, the purpose of this study was to evaluate the ability of 4-HNE to modulate IL-6 production in isolated primary rat Kupffer cells. 4-HNE (0.1–10 M) reduced both lipopolysaccharide (LPS)-induced IL-6 pro-tein production and mRNA levels. The role of nuclear factor-B (NF-B) in IL-6 induction was elucidated using Kupffer cells transduced in vitro with a recombinant adenovirus containing a IB super-repressor resistant to phosphorylation and degra-dation (Ad5IB). Using this system, LPS-induced IL-6 protei