Abstract
Reactive oxygen species (ROS) produced in macrophages is critical for microbial killing, but they also take part in inflammation and antigen presentation functions. MicroRNAs (miRNAs) are endogenous regulators of gene expression, and they can control immune responses. To dissect the complex nature of ROS-mediated effects in macrophages, we sought to characterize miRNAs that are responsive to oxidative stress-induced with hydrogen peroxide (H2O2) in the mouse macrophage cell line, RAW 264.7. We have identified a set of unique miRNAs that are differentially expressed in response to H2O2. These include miR-27a*, miR-27b*, miR-29b*, miR-24-2*, and miR-21*, all of which were downregulated except for miR-21*. By using luciferase reporter vector containing nuclear factor-kB (NF-kB) response elements, we demonstrate that overexpression of miR-27b* suppresses lipopolysaccharide-induced activation of NF-kB in RAW 264.7 cells. Our data suggest that macrophage functions can be regulated by oxidative stress-responsive miRNAs by modulating the NF-kB pathway.
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Acknowledgments
We thank Dr. Gustavo Delhon for critically reading the manuscript. This work was supported by the COBRE Program from the National Center for Research Resources (P20-RR-17675, NIH), Redox Biology Center, University of Nebraska-Lincoln. The UNMC Microarray Core Facility receives partial support from the NIH grant number P20 RR016469 from the INBRE Program of the National Center for Research Resources.
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Sivasubramani Thulasingam and Chandirasegaran Massilamany contributed equally to this work.
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Thulasingam, S., Massilamany, C., Gangaplara, A. et al. miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells. Mol Cell Biochem 352, 181–188 (2011). https://doi.org/10.1007/s11010-011-0752-2
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DOI: https://doi.org/10.1007/s11010-011-0752-2