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J Biol Chem. 2013 Feb 8;288(6):4310-20. doi: 10.1074/jbc.M112.351197. Epub 2012 Nov 26.

A newly identified microRNA, mmu-miR-7578, functions as a negative regulator on inflammatory cytokines tumor necrosis factor-α and interleukin-6 via targeting Egr1 in vivo.

Author information

1
Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Abstract

Appropriate innate immune responses are required to protect an organism against foreign pathogens, and the immune response must be tightly controlled. Here, we report a new microRNA (miRNA) identified from a small RNA library from the epididymis, termed miR-7578, that acts as a negative regulator of inflammatory responses. It was abundantly expressed in immune-related organs and induced by lipopolysaccharide in the lung and epididymis, as well as macrophages stimulated with diverse Toll-like receptor ligands, in an NF-κB-dependent manner. mmu-miR-7578 inhibited the release of pro-inflammatory cytokines, including TNFα and IL6, by regulating its target gene Egr1, which encodes a transcription factor that activates TNFα and NF-κB expression. Transgenic mice overexpressing mmu-miR-7578 displayed higher resistance to endotoxin shock and lower plasma levels of TNFα and IL6, indicating that this miRNA acted as a negative molecule of immune response. In sum, we report a previously uncharacterized LPS-responsive miRNA that controls inflammatory response in a feedback loop by fine-tuning a key transcription factor in vivo.

PMID:
23184950
PMCID:
PMC3567682
DOI:
10.1074/jbc.M112.351197
[Indexed for MEDLINE]
Free PMC Article

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