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KMID : 0578320110320030251
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Molecules and Cells
2011 Volume.32 No. 3 p.251 ~ p.255
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TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways
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Jang Young-Saeng
Kim Jae-Hee
Seo Goo-Young
Kim Pyeung-Hyeun
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Abstract
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A proliferation-inducing ligand (APRIL), a new TNF fam-ily 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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KEYWORD
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APRIL, CREB, p38 MAPK, Smad3/4, TGF-β1
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