Resolution lipoxins

Serhan and Levy, in the context of the mechanisms carried out to control the inflammatory processes, cover the latest results regarding the effects of the novel class of endogenous anti-inflammatory lipid mediators that include lipoxin, 15-epi-lipoxin and related molecules. These products are generated to dampen the host response, to prevent neutrophil-mediated tissue injury and to orchestrate resolution. Lipoxins and related analogs represent useful tools to evaluate the potential of pharmacological manipulation of the inflammatory process as a means to develop new and selective anti-inflammatory therapies with reduced unwanted toxic side effects. I am sure we will hear more and more about these lipids in the future. 

Serhan, CN and Chiang, N (2002) Lipid-derived mediators in endogenous anti-inflammation and resolution lipoxins and aspirin-triggered 15-epi-lipoxins. ScientificWorldJoumal, 2, 169-204. 

Serhan C. N. (2005a). Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot. Essent. Fatty Acids 73 141-162. 

Lipoxins are a series of anti-inflammatory, nonclassic eicosanoids ( nonclassic in the sense that they are synthesised by oxygenation of 20-carbon fatty acids other than the classic eicosanoids) whose appearance in inflammation normally signals its resolution. At present two hpoxins have been identified lipoxin A4 (LXA4) and lipoxin B4 (LXB4). 

Fig. 1 Proposed homeostatic regulation of inflammation in effective host defence. The initial phase of inflammation is initiated by a host of pro-inflammatory cytokines and eicosanoids which subsequently become diminished with time, and are coupled with the likely activation of anti-inflammatory and pro-resolution mediators, including the lipoxins, resolvins and protectins. Typically, IL 13 up-regulates 15-LO gene expression of human blood monocytes for example (Nassar et al. 1994). The associated increase in enzyme activity results in an increase in LX generation which promotes the resolution phase of inflammation. IL, interleukin TNF-a, tumour necrosis factor-a MCP-1, monocyte chemotactic protein-1 RANTES, regulated upon activation, normal T-cell expressed and secreted TGF i, transforming growth factor...

McMahon B, Mitchell S, Brady HR, Godson C (2001) Lipoxins revelations on resolution. Trends Pharmacol Sci 22 391-395... 

Serhan CN (2002) Lipoxins and aspirin-triggered 15-epi-Upoxin biosynthesis an update and role in antiinflammation and pro-resolution. Prostaglandins Other Lipid Medial 68-69 433-455... 

Bandeira-Melo C, Serra ME, Diaz BL, Cordeiro RSB, Silva PMR, Lenzi HL, Bakhle YS, Serhan CN, Martins MA Cyclooxygenase-2-derived prostaglandin Ej and lipoxin A4 accelerate resolution of allergic edema in Angiostrongylus costaricensis-infected rats Relationship with concurrent eosinophilia. J Immunol 2000 164 1029-1036. 

This chapter summarizes recent findings involving the formation and biological roles of several new types of polyunsaturated anti-inflammatory and pro-resolving lipid mediators [1], such as lipoxins, resolvins, protectins, and maresins (MaR). These molecules are able to dampen the inflammatory response, promote the resolution of inflammation, and exhibit other beneficial actions at inflammatory sites [2-4]. 

El Kebir D., Jozsef L., Pan W., Wang L., Petasis N. A., Serhan C. N., Filep J. G. 2009. 15-Epi-lipoxin A4 inhibits myeloperoxidase signaling and enhances resolution of acute lung injury. American Journal of Respiratory and Critical Care Medicine 180(4) 311-319. 

Fierro, IM and Serhan, CN (2001) Mechanisms in anti-inflammation and resolution the role of lipoxins and aspirin-triggered lipoxins. Braz J Med Biol Res, 34, 555-566. 

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