An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses
| Autor: | Yvette Garcia-Flores, Arnav Mehta, Kevin Y. Lee, David Baltimore, Jimmy L. Zhao, Li-Fan Lu, Mati Mann, Georgi K. Marinov, Alexander Y. Rudensky |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science General Physics and Astronomy Inflammation Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Mediator Immunity microRNA medicine Macrophage lcsh:Science Psychological repression Multidisciplinary HEK 293 cells NF-κB General Chemistry Cell biology 030104 developmental biology chemistry 030220 oncology & carcinogenesis Immunology lcsh:Q medicine.symptom |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-13 (2017) Nature Communications BASE-Bielefeld Academic Search Engine |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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