title: TGF-β1 stimulates mouse macrophages to express APRIL through Smad and p38MAPK/CREB pathways.
abstract: 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.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Chuncheon 200-701, Korea.
authors.forename: Young-Saeng
authors.initials: YS
authors.lastname: Jang
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Goo-Young
authors.initials: GY
authors.lastname: Seo
authors.forename: Pyeung-Hyeun
authors.initials: PH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010957:Plasmids; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C491959:Tnfsf13 protein, mouse; D053773:Transforming Growth Factor beta1; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048051:p38 Mitogen-Activated Protein Kinases