MafB is a downstream target of the IL-10/STAT3 signaling pathway, involved in the regulation of macrophage de-activation

作者：Gemelli Claudia^*; Marani Tommaso Zanocco; Bicciato Silvio; Mazza Emilia M C; Boraschi Diana; Salsi Valentina; Zappavigna Vincenzo; Parenti Sandra; Selmi Tommaso; Tagliafico Enrico; Ferrari Sergio; Grande Alexis

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2014, 1843(5): 955-964.

DOI：10.1016/j.bbamcr.2014.01.021

• MafB
• Gene regulation
• MMP9
• IL7R
• Monocyte activation
• IL-10/STAT3 pathway

In spite of the numerous reports implicating MafB transcription factor in the molecular control of monocytemacrophage differentiation, the precise genetic program underlying this activity has been, to date, poorly understood. To clarify this issue, we planned a number of experiments that were mainly conducted on human primary macrophages. In this regard, a preliminary gene function study, based on MafB inactivation and over-expression, indicated MMP9 and IL-7R genes as possible targets of the investigated transcription factor. Bioinformatics analysis of their promoter regions disclosed the presence of several putative MARE elements and a combined approach of EMSA and luciferase assay subsequently demonstrated that expression of both genes is indeed activated by MafB through a direct transcription mechanism. Additional investigation, performed with similar procedures to elucidate the biological relevance of our observation, revealed that MafB is a downstream target of the IL-10/STAT3 signaling pathway, normally inducing the macrophage de-activation process. Taken together our data support the existence of a signaling cascade by which stimulation of macrophages with the IL-10 cytokine determines a sequential activation of STAT3 and MafB transcription factors, in turn leading to an upregulated expression of MMP9 and IL-7R genes.

• 出版日期2014-5