Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programs that enable inflamed tissues to return to homeostasis. The mechanisms by which acute inflammation is resolved are of interest, and research in recent years has uncovered new endogenous anti-inflammatory and pro-resolving lipid mediators (i.e., lipoxins, resolvins, protectin, and maresin) generated from polyunsaturated fatty acids (PUFAs). This review presents new insights into the cellular and molecular mechanisms of inflammatory resolution, especially the roles of eosinophils, and a series of omega-3 PUFA-derived anti-inflammatory lipid mediators that they generate.
Lipid mediators play important roles in regulating inflammatory responses and tissue homeostasis. Since 12/15‐lipoxygenase (12/15‐LOX)‐derived lipid mediators such as lipoxin A4 (LXA4) and protectin D1 (PD1) protect against corneal epithelial cell damage, the major cell types that express 12/15‐LOX and contribute to the corneal wound healing process are of particular interest. Here, we found that eosinophils were the major cell type expressing 12/15‐LOX during the corneal wound healing process. Eosinophils were recruited into the conjunctiva after corneal epithelium wounding, and eosinophil‐deficient and/or eosinophil‐specific 12/15‐LOX knockout mice showed delayed corneal wound healing compared with wild‐type mice. Liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based mediator lipidomics revealed that a series of 12/15‐LOX‐derived mediators were significantly decreased in eosinophil‐deficient mice and topical application of 17‐hydroxydocosahexaenoic acid (17‐HDoHE), a major 12/15‐LOX‐derived product, restored the phenotype. These results indicate that 12/15‐LOX‐expressing eosinophils, by locally producing pro‐resolving mediators, significantly contribute to the corneal wound healing process in the eye.
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