양철수
2017-03-07T04:48:23Z
2017-03-07T04:48:23Z
2015-06
JOURNAL OF IMMUNOLOGY, v. 194, NO 11, Page. 5355-5365
0022-1767
1550-6606
http://www.jimmunol.org/content/194/11/5355
http://hdl.handle.net/20.500.11754/25892
MicroRNAs (miRNAs) are small noncoding nucleotides that play critical roles in the regulation of diverse biological functions, including the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis. Although the pathways associated with autophagy must be tightly regulated at a posttranscriptional level, the contribution of miRNAs and whether they specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that M. tuberculosis infection of macrophages leads to increased expression of miRNA-125a-3p (miR-125a), which targets UV radiation resistance-associated gene (UVRAG), to inhibit autophagy activation and antimicrobial responses to M. tuberculosis. Forced expression of miR-125a significantly blocked M. tuberculosis-induced activation of autophagy and phagosomal maturation in macrophages, and inhibitors of miR-125a counteracted these effects. Both TLR2 and MyD88 were required for biogenesis of miR-125a during M. tuberculosis infection. Notably, activation of the AMP-activated protein kinase significantly inhibited the expression of miR-125a in M. tuberculosisinfected macrophages. Moreover, either overexpression of miR-125a or silencing of UVRAG significantly attenuated the antimicrobial effects of macrophages against M. tuberculosis. Taken together, these data indicate that miR-125a regulates the innate host defense by inhibiting the activation of autophagy and antimicrobial effects against M. tuberculosis through targeting UVRAG.
This work was supported by National Research Foundation of Korea Grant 2007-0054932 funded by the Korean government (Ministry of Science, ICT and Future Planning) at Chungnam National University and by National Research Foundation of Korea Grant 2011-0027459 funded by the Korean government (Ministry of Education and Science Technology).
en
AMER ASSOC IMMUNOLOGISTS
PHAGOSOME MATURATION
DEFENSE-MECHANISM
PROTEIN-KINASE
HOST-DEFENSE
TUBERCULOSIS
PATHWAY
IMMUNITY
TARGETS
SYSTEM
CELLS
MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection
Article
11
194
10.4049/jimmunol.1402557
5355-5365
JOURNAL OF IMMUNOLOGY
Kim, Jin Kyung
Yuk, Jae-Min
Kim, Soo Yeon
Kim, Tae Sung
Jin, Hyo Sun
Yang, Chul-Su
Jo, Eun-Kyeong
2015003628
S
GRADUATE SCHOOL[S]
DEPARTMENT OF BIONANOTECHNOLOGY
chulsuyang