Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells.

Activation of Kupffer cells is a prominent feature of necro-inflammatory liver injury. We have recently demonstrated that 5-lipoxygenase (5-LO) and its accessory protein, 5-LO-activating protein (FLAP), are essential for the survival of Kupffer cells in culture, as their inhibition drives these liver resident macrophages to programmed cell death. In the current study, we explored whether the potent FLAP inhibitor, Bay-X-1005, reduces the number of Kupffer cells in vivo and whether this pharmacological intervention protects the liver from carbon tetrachloride (CCl(4))-induced damage.

Aspirin (ASA) regulates 5-lipoxygenase activity and peroxisome proliferator-activated receptor alpha-mediated CINC-1 release in rat liver cells: novel actions of lipoxin A4 (LXA4) and ASA-triggered 15-epi-LXA4.

The mechanism of action of aspirin (ASA) is related to cyclooxygenase (COX) inhibition, but additional actions cannot be excluded for their antiinflammatory properties and antithrombotic activity. In the current investigation, we examined the effects of ASA on COX and 5-lipoxygenase (5-LO) pathways and its impact on peroxisome proliferator-activated receptor alpha (PPARalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels in rat liver cells. In Kupffer cells, the liver resident macrophages, ASA switched eicosanoid biosynthesis from prostaglandin E2 (PGE2) to leukotriene B4 (LTB4) and 15-epi-lipoxin A4 (15-epi-LXA4) formation.