老年学と老年医学の研究

概要

Immunoresolving Lipid Mediators and Resolution of Inflammation in Aging

Antonio Recchiuti, Joan Claria, Matthew Spite and Bruce D Levy

Unresolved inflammation is associated with several widely recurrent aging-associated diseases such as arthritis, periodontitis, metabolic disorders, atherosclerosis, and neurodegeneration. Endogenous mechanisms that curtail excessive inflammation and prompt its timely resolution are of considerable interest. In recent years, previously unrecognized chemical mediators derived from polyunsaturated fatty acids were identified as endogenous specialized pro-resolving lipid mediators (SPM) that control both the magnitude and duration of acute inflammation and activate resolution. Lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (Mar) are possess distinct chemical structures, bind to specific G-protein coupled receptors (GPCRs) in a stereospecific manner, and regulate biological pathways to promote resolution in several pre-clinical experimental settings of age-related inflammatory diseases. This review highlights the biosynthesis of SPM and cellular mechanisms that underscore their beneficial bioactions in the regulation of acute inflammation in age-related diseases. The elucidation of these mechanisms operating in vivo to keep acute inflammation under physiologic boundaries and stimulate resolution opened many new opportunities in resolution pharmacology to target aging-associated chronic inflammatory pathologies.