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


Journal of Clinical & Cellular Immunology

Author(s): Imaizumi T, Tanaka H, Tajima A, Yokono Y, Matsumiya T,

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Abstract 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. 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. 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. Copyright © 2010 S. Karger AG, Basel. This article was published in Am J Nephrol and referenced in Journal of Clinical & Cellular Immunology

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