Abstract
MicroRNAs are key regulators of many biological processes, including cell differentiation. Here we show that during human monocyte-macrophage differentiation, expression of the microRNAs miR-223, miR-15a and miR-16 decreased considerably, which led to higher expression of the serine-threonine kinase IKKα in macrophages. In macrophages, higher IKKα expression in conjunction with stabilization of the kinase NIK induced larger amounts of p52. Because of low expression of the transcription factor RelB in untreated macrophages, high p52 expression repressed basal transcription of both canonical and noncanonical NF-κB target genes. However, proinflammatory stimuli in macrophages resulted in greater induction of noncanonical NF-κB target genes. Thus, a decrease in certain microRNAs probably prevents macrophage hyperactivation yet primes the macrophage for certain responses to proinflammatory stimuli.
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Acknowledgements
We thank the Preclinical Repository of the National Cancer Institute for the antibody to the p100 C terminus and the National Institutes of Health Blood Bank for elutriated monocytes. Supported by the Intramural Research Program of The Center for Cancer Research, National Cancer Institute, National Institutes of Health.
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T.L. and M.J.M. contributed equally to this work and are listed alphabetically; all authors contributed throughout each stage of the development of the manuscript (conception, design, experiments and analysis).
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Li, T., Morgan, M., Choksi, S. et al. MicroRNAs modulate the noncanonical transcription factor NF-κB pathway by regulating expression of the kinase IKKα during macrophage differentiation. Nat Immunol 11, 799–805 (2010). https://doi.org/10.1038/ni.1918
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DOI: https://doi.org/10.1038/ni.1918
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