[PDF][PDF] Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators

Y Li, J Dalli, N Chiang, RM Baron, C Quintana… - Immunity, 2013 - cell.com
Immunity, 2013cell.com
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 …
Summary
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.
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