IFN-γ and TNF-α Synergistically Induce microRNA-155 Which Regulates TAB2/IP-10 Expression in Human 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. Methods: The expression of miR-155 in cultured normal human mesangial cells treated with interferon-gamma (IFN-gamma) and/or tumor-necrosis factor-alpha (TNF-alpha) was examined. The cells were transfected with miR-155 mimic, siRNA against transforming growth factor-beta-activated kinase-1 (TAK1)-binding protein 2 (TAB2) or siRNA against nuclear factor-kappa B (NF-kappa B). Results: IFN-gamma and TNF-alpha synergistically induced the expression of miR-155. Transfection of cells with miR-155 mimic inhibited the expression of TAB2 and IFN-gamma-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-kappa B. Conclusion: Combined stimulation with IFN-gamma and TNF-alpha induces miR-155 via TAB2 and NF-kappa B. 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 (C) 2010 S. Karger AG, Basel