IFN-γ and TNF-α synergistically induce microRNA-155 which regulates TAB2/IP-10 expression in human mesangial cells.
OBJECTIVE
MicroRNAs are noncoding small RNA molecules that posttranscriptionally regulate gene expression. microRNA-155 (miR-155), one of the microRNAs, is involved in the control of various genes. However, the role of miR-155 in inflammatory responses in mesangial cells is not known. In the present study, we examined the expression of miR-155 in mesangial cells.


METHODS
The expression of miR-155 in cultured normal human mesangial cells treated with interferon-γ (IFN-γ) and/or tumor-necrosis factor-α (TNF-α) was examined. The cells were transfected with miR-155 mimic, siRNA against transforming growth factor-β-activated kinase-1 (TAK1)-binding protein 2 (TAB2) or siRNA against nuclear factor-κB (NF-κB).


RESULTS
IFN-γ and TNF-α synergistically induced the expression of miR-155. Transfection of cells with miR-155 mimic inhibited the expression of TAB2 and IFN-γ-inducible protein of 10 kDa (IP-10). The expression of IP-10 was suppressed by knockdown of TAB2. Induction of miR-155 was inhibited by RNA interference against TAB2 or NF-κB.


CONCLUSIONS
Combined stimulation with IFN-γ and TNF-α induces miR-155 via TAB2 and NF-κB. miR-155 negatively regulates TAB2, as a negative feedback system, to lower IP-10 expression. miR-155 may play a role in the regulation of inflammatory and immune reactions in the kidney.
Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. timaizum@cc.hirosaki-u.ac.jp
Tadaatsu
T
Imaizumi
Hiroshi
H
Tanaka
Atsushi
A
Tajima
Yoshikazu
Y
Yokono
Tomoh
T
Matsumiya
Hidemi
H
Yoshida
Kazushi
K
Tsuruga
Tomomi
T
Aizawa-Yashiro
Ryo
R
Hayakari
Ituro
I
Inoue
Etsuro
E
Ito
Kei
K
Satoh
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics* / Q000378:metabolism; D004357:Drug Synergism; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics* / Q000494:pharmacology; D050527:Mesangial Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D054357:Chemokine CXCL10; D018836:Inflammation Mediators; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C410585:TAB2 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma