期刊
Nature Microbiology
卷 1, 期 10, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMICROBIOL.2016.132
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资金
- National Institutes of Health [AI109317-01A1, AI101973-01]
- National 973 Basic Research Program of China [2013CB911300]
- Chinese NSFC [81225015, 81430071]
- Sichuan Science-Technology Innovative Research Team for Young Scientist [2013TD0001]
MicroRNAs (miRNAs) play critical roles in various biological processes, including cell proliferation, development and host defence. However, the molecular mechanism for miRNAs in regulating bacterial-induced inflammation remains largely unclear. Here, we report that miR-301b augments pro-inflammatory response during pulmonary infection, and caffeine suppresses the effect of miR-301b and thereby augments respiratory immunity. LPS treatment or Pseudomonas aeruginosa infection induces miR-301b expression via a TLR4/MyD88/NF-kappa B pathway. Importantly, caffeine decreases miR-301b expression through negative regulation of the cAMP/PKA/NF-kappa B axis. Further, c-Myb is identified as a target of miR-301b, which positively modulates anti-inflammatory cytokines IL-4 and TGF-beta 1, but negatively regulates pro-inflammatory cytokines MIP-1 alpha and IL-17A. Moreover, repression of miR-301b results in increased transcription of c-Myb and elevated levels of neutrophil infiltration, thereby alleviating infectious symptoms in mice. These findings reveal miR-301b as a new controller of inflammatory response by repressing c-Myb function to inhibit the anti-inflammatory response to bacterial infection, representing a novel mechanism for balancing inflammation.
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