[HTML][HTML] Lovastatin decreases acute mucosal inflammation via 15-epi-lipoxin A4

A Planagumā, MA Pfeffer, G Rubin, R Croze… - Mucosal …, 2010 - nature.com
A Planagumā, MA Pfeffer, G Rubin, R Croze, M Uddin, CN Serhan, BD Levy
Mucosal immunology, 2010nature.com
The widespread use of statins for hypercholesterolemia has uncovered pleiotropic anti-
inflammatory properties that were unexpected based on the drugs' original design; yet,
mechanisms for these protective actions remain uncertain. In this study lovastatin triggered
biosynthesis of the anti-inflammatory and pro-resolving mediator 15-epi-lipoxin A 4 (15-epi-
LXA 4). During interactions between human neutrophils and airway epithelial cells, the statin-
induced increase in 15-epi-LXA 4 was associated with increased 14, 15 …
Abstract
The widespread use of statins for hypercholesterolemia has uncovered pleiotropic anti-inflammatory properties that were unexpected based on the drugs' original design; yet, mechanisms for these protective actions remain uncertain. In this study lovastatin triggered biosynthesis of the anti-inflammatory and pro-resolving mediator 15-epi-lipoxin A 4 (15-epi-LXA 4). During interactions between human neutrophils and airway epithelial cells, the statin-induced increase in 15-epi-LXA 4 was associated with increased 14, 15-epoxyeicosatrienoic acid (14, 15-EET) generation. When added to activated neutrophils, 14, 15-EET enhanced 15-epi-LXA 4 biosynthesis. In a murine model of airway mucosal injury and inflammation, lovastatin increased 15-epi-LXA 4 formation in vivo and markedly decreased acute lung inflammation. Administration of 15-epi-LXA 4 also inhibited lung inflammation in an additive manner with lovastatin. Together, these results indicate that statin-triggered 15-epi-LXA 4 generation during human leukocyte–airway epithelial cell interactions is an endogenous mechanism for statin-mediated tissue protection at mucosal surfaces that may also be relevant in the statins' ability to stimulate the resolution of inflammation.
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