| First Author | Mann M | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 851 |
| PubMed ID | 29021573 | Mgi Jnum | J:252730 |
| Mgi Id | MGI:6099128 | Doi | 10.1038/s41467-017-00972-z |
| Citation | Mann M, et al. (2017) An NF-kappaB-microRNA regulatory network tunes macrophage inflammatory responses. Nat Commun 8(1):851 |
| abstractText | The innate inflammatory response must be tightly regulated to ensure effective immune protection. NF-kappaB 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-kappaB activity in mouse macrophages. Elevated miR-155 expression potentiates NF-kappaB 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-kappaB 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-kappaB 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-kappaB signalling, miR-155 and miR-146a form a complex network of cross-regulations to control gene transcription in macrophages for modulating inflammatory responses. |
