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Mol. Cells 2011; 32(3): 251-255
Published online June 23, 2011
https://doi.org/10.1007/s10059-011-1040-4
© The Korean Society for Molecular and Cellular Biology
TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways
Young-Saeng Jang1, Jae-Hee Kim1, Goo-Young Seo1, and Pyeung-Hyeun Kim1,2,*
Correspondence to : *Correspondence: phkim@kangwon.ac.kr
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.
Keywords APRIL, CREB, p38 MAPK, Smad3/4, TGF-β1
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Research Article
Mol. Cells 2011; 32(3): 251-255
Published online September 30, 2011 https://doi.org/10.1007/s10059-011-1040-4
Copyright © The Korean Society for Molecular and Cellular Biology.
TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways
Young-Saeng Jang1, Jae-Hee Kim1, Goo-Young Seo1, and Pyeung-Hyeun Kim1,2,*
1Department of Molecular Bioscience, College of Biomedical Science, Chuncheon 200-701, Korea, 2Medical and Bio-Material Research Center, Kangwon National University, Chuncheon 200-701, Korea
Correspondence to:*Correspondence: phkim@kangwon.ac.kr
Abstract
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.
Keywords: APRIL, CREB, p38 MAPK, Smad3/4, TGF-β1
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