C/EBPbeta mediates synergistic upregulation of gene expression by interferon-gamma and tumor necrosis factor-alpha in bone marrow-derived mesenchymal stem cells.

ABSTRACT: Mesenchymal stem cells (MSCs) are potent immunoregulators and have shown clinical utility in suppressing immunity. MSC function is modulated by cytokines, since inflammatory cytokines, such as interferon-gamma (IFNgamma) concomitant with tumor necrosis factor-alpha (TNFalpha), induce their immunoregulatory capability. Here, we show that IFNgamma and TNFalpha act synergistically to induce high levels of expression of interleukin-6 (IL-6) and several other immune-related molecules in MSCs in vitro. We further found that, while either IFNgamma or TNFalpha alone induced minor expression of C/EBPbeta in MSCs, this transcription factor was dramatically upregulated when these cytokines were added together. A causal relationship between C/EBPbeta upregulation and IL-6 expression was demonstrated b

SUBMITTER: Xu G 

PROVIDER: S-EPMC3412173 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature