Lipoxins in gastric mucosal health and disease.
Lipoxins have well characterized anti-inflammatory properties. In recent years, lipoxin A4 and its epimeric counterpart, which is synthesized via aspirin-acetylated cyclooxygenase-2, have been shown to exert very potent protective effects in the stomach. Indeed, suppression of aspirin-triggered lipoxin synthesis, through co-administration of a selective COX-2 inhibitor, results in a significant exacerbation of gastric injury. The gastroprotective effects of lipoxin A4 appear to be receptor mediated, and may be attributable to the ability of this agent to suppress leukocyte adherence to the vascular endothelium and to elevate gastroduodenal blood flow. These effects may be mediated via lipoxin-induced nitric oxide generation. Lipoxins activate a receptor that can also be activated by annexin-1, another substance involved in resolution of inflammation and gastroprotection.
Wallace
John L
JL
Mucosal Inflammation Research Group, Department of Pharmacology and Therapeutics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alta., Canada T2N 4N1. wallacej@ucalgary.ca
de Lima
Octavio Menezes
OM
Fiorucci
Stefano
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D005756:Gastritis / Q000628:therapy*; D007962:Leukocytes / Q000502:physiology; D044045:Lipoxins / Q000096:biosynthesis / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; C040527:lipoxin A4; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D001241:Aspirin