Anti-inflammatory circuitry: lipoxin, aspirin-triggered lipoxins and their receptor ALX.
Endogenous chemical mediators or autacoids play key roles in controlling inflammation and its programmed resolution. Among them, it is known that lipoxins (LX) and aspirin-triggered LX (ATL) evoke bioactions in a range of physiologic and pathophysiologic processes and serve as endogenous lipid/chemical mediators that stop neutrophilic infiltration and initiate resolution. LXA4, ATL and their metabolic stable analogs elicit cellular responses and regulate PMN in vivo via interacting with their specific receptor, namely ALX. ALX is the first cloned and identified lipoxygenase-derived eicosanoid receptor with cell type-specific signaling pathways. Also, ALX could regulate PMN by interacting with each class of ligands (lipid vs. peptide) within specific phases of an inflammatory response. Together LX, ATL and ALX may provide new opportunities to design "resolution-targeted" therapies with high degree of precision in controlling inflammation. In this chapter, we give an overview and update of the current actions for LX and ATL, the identification of ALX and their novel anti-inflammatory and pro-resolving signals.
Chiang
Nan
N
The Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. nchiang@zeus.bwh.harvard.edu
Arita
Makoto
M
Serhan
Charles N
CN
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D044045:Lipoxins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D044067:Receptors, Lipoxin / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D044067:Receptors, Lipoxin; D001241:Aspirin