RGD Reference Report - microRNA-146a promotes mycobacterial survival in macrophages through suppressing nitric oxide production. - Rat Genome Database

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microRNA-146a promotes mycobacterial survival in macrophages through suppressing nitric oxide production.

Authors: Li, Miao  Wang, Jinli  Fang, Yimin  Gong, Sitang  Li, Meiyu  Wu, Minhao  Lai, Xiaomin  Zeng, Gucheng  Wang, Yi  Yang, Kun  Huang, Xi 
Citation: Li M, etal., Sci Rep. 2016 Mar 30;6:23351. doi: 10.1038/srep23351.
RGD ID: 126925155
Pubmed: PMID:27025258   (View Abstract at PubMed)
PMCID: PMC4812255   (View Article at PubMed Central)
DOI: DOI:10.1038/srep23351   (Journal Full-text)

Macrophages play a crucial role in host innate anti-mycobacterial defense, which is tightly regulated by multiple factors, including microRNAs. Our previous study showed that a panel of microRNAs was markedly up-regulated in macrophages upon mycobacterial infection. Here, we investigated the biological function of miR-146a during mycobacterial infection. miR-146a expression was induced both in vitro and in vivo after Mycobacterium bovis BCG infection. The inducible miR-146a could suppress the inducible nitric oxide (NO) synthase (iNOS) expression and NO generation, thus promoting mycobacterial survival in macrophages. Inhibition of endogenous miR-146a increased NO production and mycobacterial clearance. Moreover, miR-146a attenuated the activation of nuclear factor κB and mitogen-activated protein kinases signaling pathways during BCG infection, which in turn repressed iNOS expression. Mechanistically, miR-146a directly targeted tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) at post-transcriptional level. Silencing TRAF6 decreased iNOS expression and NO production in BCG-infected macrophages, while overexpression of TRAF6 reversed miR-146a-mediated inhibition of NO production and clearance of mycobacteria. Therefore, we demonstrated a novel role of miR-146a in the modulation of host defense against mycobacterial infection by repressing NO production via targeting TRAF6, which may provide a promising therapeutic target for tuberculosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Mycobacterium Infections  ISOMir146 (Mus musculus)126925155; 126925155miRNA:altered expression:peritoneum and liver (mouse)RGD 
Mycobacterium Infections  IEP 126925155miRNA:altered expression:peritoneum and liver (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir146a  (microRNA 146a)

Genes (Mus musculus)
Mir146  (microRNA 146)

Genes (Homo sapiens)
MIR146A  (microRNA 146a)


Additional Information