Plasticity of Leukocytic Exudates in Resolving Acute Inflammation Is Regulated by MicroRNA and Proresolving Mediators

• Published in: Immunity (Cambridge, Mass.) Vol. 39; no. 5; pp. 885 - 898
• Main Authors: Li, Yongsheng, Dalli, Jesmond, Chiang, Nan, Baron, Rebecca M., Quintana, Carolina, Serhan, Charles N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.11.2013; Elsevier Limited
• Subjects: Acute Disease; Animals; Apoptosis; Biosynthesis; Chemotaxis - physiology; Docosahexaenoic Acids - metabolism; Gene expression; Gene Expression Regulation; Human subjects; Humans; Inflammation Mediators - metabolism; Leukocytes; Macrophages - metabolism; Male; Mice; MicroRNAs - biosynthesis; MicroRNAs - genetics; MicroRNAs - physiology; Neutrophils - metabolism; NF-kappa B - metabolism; Peritonitis - chemically induced; Peritonitis - immunology; Peritonitis - metabolism; Peritonitis - pathology; Phagocytosis - physiology; Sepsis; Sepsis - blood; Sepsis - mortality; Transcription Factor AP-1 - metabolism; Transcription, Genetic; Zymosan - toxicity
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.10.011

The magnitude and duration of acute inflammation are controlled by active resolution programs involving specialized proresolving mediators (SPMs; resolvins and maresins) and microRNAs (miRNAs). Here, we report that miR-466l was temporally regulated in murine exudate-infiltrating leukocytes. Neutrophil miR-466l overexpression in vivo promoted initiation of inflammation that anteceded macrophage expression of this miRNA, which accelerated resolution when overexpressed. In macrophages, miR-466l overexpression increased prostanoids and SPMs (e.g., resolvin D1 [RvD1] and RvD5), which enhanced resolution. RvD1, RvD2, maresin 1 (MaR1), and apoptotic neutrophils reduced miR-466l expression within human macrophages, a feedback regulation that most likely prepares for homeostasis. miR-466l was upregulated in peripheral blood of sepsis patients, and its increase correlated with nonsurvival from sepsis. SPMs and miR-466l regulated transcription factors activator protein 1 and nuclear factor κB1 in miRNA biogenesis. These results demonstrate pivotal roles for SPMs and miR-466l in dynamic leukocyte plasticity during resolution of acute inflammatory responses. [Display omitted] •Acute inflammation upregulates miR-466l, which regulates resolution•Overexpression of miR-466l promotes specialized proresolving mediator production•Resolvin D1 and miR-466l each enhance efferocytosis, contributing to resolution•miR-466l is present and increased in sepsis nonsurvivors