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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow.

The main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cycloxygenases COX-1 and COX-2. During recent years, combined 5-LOX/COX-inhibition, interfering with the biosynthesis of both prostaglandins and leukotrienes (LTs), has emerged as a possibility to avoid side effects related to COX-inhibition. The aim of the present study was to investigate if there is a contribution of mechanisms other than the reduction of inflammatory prostaglandins and leukotrienes to the anti-inflammatory effect of the LOX/COX inhibitor licofelone. In a flow chamber assay, licofelone (10-30 microM) dose-dependently decreased both the rolling and adhesion of leukocytes on endothelial cells (EC). In contrast, no effects were found after treatment of EC with the unselective COX-1/ COX-2 inhibitor indomethacin (30 microM), the potent and selective 5-LOX inhibitor, ZD-2138 (30 microM), the mainly COX-2 inhibitor aceclofenac (30 microM), the selective COX-2 inhibitor celecoxib (30 microM) and the combination of ZD-2138 with the selective COX-2 inhibitor celecoxib (30 microM). In the presence of licofelone (30 microM) the expression of E-selectin mRNA in cytokine-stimulated EC was attenuated, whereas no NSAID (30 microM) tested showed any effect on E-selectin expression. Moreover, licofelone treatment (30 microM) attenuated expression of VCAM-1 and ICAM-1 on inflammatory EC. The effect of licofelone on leukocyte recruitment was also evaluated in vivo. Using a mouse peritonitis model it was found that leukocyte accumulation was markedly reduced in licofelone treated animals (100mg/kg) compared to untreated mice. Thus, the novel 5-LOX/COX inhibitor licofelone possesses anti-inflammatory activity that, in addition to COX/ LOX inhibition, involves effects on leukocyte-endothelial interactions.[1]

References

  1. Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow. Ulbrich, H., Soehnlein, O., Xie, X., Eriksson, E.E., Lindbom, L., Albrecht, W., Laufer, S., Dannhardt, G. Biochem. Pharmacol. (2005) [Pubmed]
 
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