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Mol Cells. 2011 Sep;32(3):251-5. doi: 10.1007/s10059-011-1040-4. Epub 2011 Jun 23.

TGF-β1 stimulates mouse macrophages to express APRIL through Smad and p38MAPK/CREB pathways.

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Department of Molecular Bioscience, College of Biomedical Science, Chuncheon 200-701, Korea.


A proliferation-inducing ligand (APRIL), a new TNF family member, supports B-cell survival and tumor cell proliferation. APRIL is secreted as a soluble protein by macrophages, dendritic cells and activated T cells. However, factors involved in regulation of APRIL expression are as yet unknown. In this study, we investigated the effect of TGF-β1 on APRIL expression in P388D1, a mouse macrophage cell line. TGF-β1 induced APRIL mRNA expression in a time- and dose-dependent manner. One nanogram per milliliter of TGF-β1 was optimal and APRIL transcripts appeared as early as 3 h after stimulation. Based on our studies, which included overexpression of Smad3, DN-Smad3, and sh-Smad3, we found that Smad3 mediates APRIL transcription at least partially. Further, experiments using inhibitors revealed that p38MAPK and CREB are also involved in TGF-β1-induced APRIL expression. These results suggest that TGF-β1, through Smad3 and p38MAPK/CREB signaling pathways, stimulates APRIL expression in macrophages.

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