Molecular analysis of TGF-β1-induced BAFF promoter activity in mouse antigen presenting cells

초록

BAFF, one of the TNF ligand family, is primarily expressed by APCs such as macrophages and dendritic cells. This molecule is known to stimulate proliferation, differentiation, survival, and Ig production of B cells. In the present study, we aimed to elucidate the molecular mechanisms by which TGF-beta 1 induce BAFF expression in order to gain a clue if TGF-beta 1 may regulate B cell differentiation through influencing APCs. We found that TGF-beta 1 potentiates mouse dendritic cells to express BAFF and that a typical TGF-beta signaling pathway is involved. Thus, Smad3 and Smad4 promoted BAFF promoter activity in mouse dendritic cells and macrophages. Further, from the analysis of the BAFF mutated promoters, we identified three putative Smad binding elements (SBEs) where Smad3 actually binds. These elements were indispensable for the promoter activity.

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