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miR-27a regulates inflammatory response of macrophages by targeting IL-10

Xie, Na, Cui, Huachun, Banerjee, Sami, Tan, Zheng, Salomao, Reinaldo, Fu, Mingui, Abraham, Edward, Thannickal, Victor J +1 more·2014·The Journal of Immunology
DOI 10.4049/jimmunol.1400203PMC PMC4065847
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Abstract

Although microRNAs were shown to participate in innate immune responses, it is not completely understood how they regulate negative immunomodulatory events. IL-10 is an important anti-inflammatory mediator that prevents excessive inflammation and associated immunological pathologies. Although the regulation of IL-10 expression has been well studied at both the transcriptional and translational levels, it is less clear how microRNAs control IL-10 expression during inflammation. In this study, we found that miR-27a is downregulated in macrophages following stimulation through TLR2 and TLR4, but not TLR3. Upregulation of miR-27a enhanced the expression of proinflammatory cytokines in TLR2/4-activated macrophages. Conversely, knockdown of miR-27a diminished cytokine expression. Mechanistically, we found that miR-27a negatively regulates IL-10 expression; upregulation of miR-27a decreases, whereas downregulation of miR-27a increases, IL-10 expression in activated macrophages. Likely due to the decreased expression of IL-10, upregulation of miR-27a diminished IL-10–dependent STAT3 phosphorylation in TLR4-activated macrophages. Consistent with IL-10 being a potential mediator for the role of miR-27a in the immune response, blocking IL-10 abolished the enhancing effect of miR-27a on TLR4-activated inflammation. In conclusion, our study identified miR-27a downregulation as a negative-regulatory mechanism that prevents overly exuberant TLR2- and TLR4-driven inflammatory responses.

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Authors
Xie, N., Cui, H., Banerjee, S., Tan, Z., Salomao, R., Fu, M., Abraham, E., Thannickal, V. J., & Liu, G.
Affiliations
  • Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294
  • Department of Medicine, Paulista School of Medicine, Federal University of Sao Paulo , Sao Paulo SP 04039 032 ,
  • Department of Basic Medical Science, University of Missouri-Kansas City , Kansas City, MO 64108
  • Wake Forest School of Medicine , Winston-Salem, NC 27157
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2014-07-01
Volume
193
Issue
1
Pages
327-334
ISSN
  • 0022-1767
  • 1550-6606
DOI
10.4049/jimmunol.1400203
PMC
PMC4065847
Cited by
120
References
4
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)

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