(23-06-09)iResolvins E1 and D1 in Choroid-retinal Endothelial Cells and Leukocytes: Biosynthesis and Mechanisms of Anti-inflammatory Actions.

Tian H, Lu Y, Sherwood AM, Hongqian D, Hong S.
Neuroscience Center, Department of Ophthalmology, LSUHSC, New Orleans, Louisiana, United States.

Purpose. 1) To investigate the biosynthesis of resolvins E1 and D1 (RvE1 and RvD1) in choroid-retinal endothelial cells (CREC) and leukocytes under inflammatory conditions; 2) To define the mechanisms of anti-inflammatory actions of RvE1 and RvD1 in CREC and leukocytes, these cells are crucial to posterior ocular inflammation. Methods. RvE1, RvD1, and markers of their biosynthesis were determined via lipidomic analysis. After CREC or cocultures of CREC and leukocytes were treated with RvE1 or RvD1 and inflammatory stimuli, inflammatory signaling molecules were quantified by Western-blot, ELISA, and/or protein array. Transmigration of polymorphonuclear leukocytes (PMN) across CREC monolayers was quantified. Results. The inflammatory stimulation increased the biosynthesis of RvE1 and RvD1 from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively, in coculture of CREC and leukocytes. CREC alone did not produce RvE1 and RvD1. RvE1 or RvD1 inhibited the expressions of vascular cell adhesion molecule-1, interleukin-8, macrophage inflammatory protein-1beta, regulated on activation normal T cell expressed and secreted, and/or tumor necrosis factor-alpha from CREC or cocultures of CREC and leukocytes. RvD1 reduced prostaglandin E2 generation from CREC. However, neither resolvin affected cyclooxygenase-2 formation. Treating CREC or PMN with RvE1 or RvD1 inhibited PMN transmigration across CREC barriers. Conclusions. The interplay of inflammatory-stimuli activated CREC and leukocytes biosynthesizes RvE1 and RvD1 from EPA and DHA. These resolvins inhibit inflammatory signaling from CREC and leukocytes as well as inflammatory activity as PMN transmigration across CREC barriers. Thus, these resolvins and their biosynthesis pathways are potential targets for novel treatment of inflammatory ocular diseases.

Source: Invest Ophthalmol Vis Sci. 2009 May 14

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