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- Title
Aspirin (ASA) regulates 5‐lipoxygenase activity and peroxisome proliferator‐activated receptor α‐mediated CINC‐1 release in rat liver cells: novel actions of lipoxin A<sub>4</sub> (LXA<sub>4</sub>) and ASA‐triggered 15‐epi‐LXA<sub>4</sub>
- Authors
Planagumà, Anna; Titos, Esther; López‐Parra, Marta; Gaya, Joan; Pueyo, Gloria; Arroyo, Vicente; Clària, Joan
- Abstract
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 α (PPARα) 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. In hepatocytes, ASA significantly inhibited PPARα protein expression and CINC‐1 secretion, effects that were also observed in hepatocytes exposed to the selective PPARα agonist Wy‐14643. In contrast, treatment of hepatocytes with PGE2 in association with LTB4 had no significant effect on PPARα but stimulated CINC‐1 release. Interestingly, the endogenous antiinflammatory eicosanoids LXA4 and ASA‐triggered 15‐epi‐LXA4, in addition to inhibiting macrophage 5‐LO activity to a similar extent as PGE2, significantly reduced PPARα and CINC‐1 levels in hepatocytes. Taken together and because arachidonic acid‐derived products, PPARα levels, and CINC‐1 secretion are involved in the extent and duration of an inflammatory response, these findings provide additional molecular mechanisms for the pharmacological properties of ASA.
- Publication
FASEB Journal, 2002, Vol 16, Issue 14, p1937
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.02-0224fje