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An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses.

An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses.
Author Information (click to view)

Mann M, Mehta A, Zhao JL, Lee K, Marinov GK, Garcia-Flores Y, Baltimore D,


Mann M, Mehta A, Zhao JL, Lee K, Marinov GK, Garcia-Flores Y, Baltimore D, (click to view)

Mann M, Mehta A, Zhao JL, Lee K, Marinov GK, Garcia-Flores Y, Baltimore D,

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Nature communications 2017 10 118(1) 851 doi 10.1038/s41467-017-00972-z
Abstract

The innate inflammatory response must be tightly regulated to ensure effective immune protection. NF-κB is a key mediator of the inflammatory response, and its dysregulation has been associated with immune-related malignancies. Here, we describe a miRNA-based regulatory network that enables precise NF-κB activity in mouse macrophages. Elevated miR-155 expression potentiates NF-κB activity in miR-146a-deficient mice, leading to both an overactive acute inflammatory response and chronic inflammation. Enforced miR-155 expression overrides miR-146a-mediated repression of NF-κB activation, thus emphasizing the dominant function of miR-155 in promoting inflammation. Moreover, miR-155-deficient macrophages exhibit a suboptimal inflammatory response when exposed to low levels of inflammatory stimuli. Importantly, we demonstrate a temporal asymmetry between miR-155 and miR-146a expression during macrophage activation, which creates a combined positive and negative feedback network controlling NF-κB activity. This miRNA-based regulatory network enables a robust yet time-limited inflammatory response essential for functional immunity.MicroRNAs (miR) are important regulators of gene transcription, with miR-155 and miR-146a both implicated in macrophage activation. Here the authors show that NF-κB signalling, miR-155 and miR-146a form a complex network of cross-regulations to control gene transcription in macrophages for modulating inflammatory responses.

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