IFN-γ and TNF-α synergistically induce microRNA-155 which regulates TAB2/IP-10 expression in human mesangial cells

IFN-γ 和 TNF-α 协同诱导 microRNA-155,从而调节人系膜细胞中的 TAB2/IP-10 表达

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作者:Tadaatsu Imaizumi, Hiroshi Tanaka, Atsushi Tajima, Yoshikazu Yokono, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Tomomi Aizawa-Yashiro, Ryo Hayakari, Ituro Inoue, Etsuro Ito, Kei Satoh

Aims

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.

Background/aims

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.

Conclusion

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.

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.

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