Activin A Stimulates Mouse APCs to Express BAFF via ALK4-Smad3 Pathway
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Background: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. Methods: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. Results: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. Conclusion: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.
Abstract
Background: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. Methods: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. Results: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. Conclusion: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.
참고문헌 (30)
- Craxton A, "Macrophage- and dendritic cell--dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF", Blood, 101, pp.4464~4471 (2003)
- Dubois B, "Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes", J Immunol, 161, pp.2223~2231 (1998)
- Dubois B, "Dendritic cells enhance growth and differentiation of CD40-activated B lymphocytes", J Exp Med, 185, pp.941~951 (1997)
- Fagarasan S, "T-Independent immune response: new aspects of B cell biology", Science, 290, pp.89~92 (2000)
- Snapper CM, "model for induction of T cell-independent humoral immunity in response to polysaccharide antigens", J Immunol, 157, pp.2229~2233 (1996)
- Groom J, "Association of BAFF", BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome, 2002, pp.109, 59~68
- Schneider P, "BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth", J Exp Med, 189, pp.1747~1756 (1999)
- Mackay F, "The TNF family members BAFF and APRIL: the growing complexity", Cytokine Growth Factor Rev, 14, pp.311~324 (2003)
- Mackay F, "BAFF: a fundamental survival factor for B cells", Nat Rev Immunol, 2, pp.465~475 (2002)
- Sutherland AP, "Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas", Pharmacol Ther, 112, pp.774~786 (2006)
- Muramatsu M, "Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme", Cell, 102, pp.553~563 (2000)
- Litinskiy MB, "DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL", Nat Immunol, 3, pp.822~829 (2002)
- Kim PH, "Transforming growth factor beta 1 increases IgA isotype switching at the clonal level", J Immunol, 145, pp.3773~3778 (1990)
- Lebman DA, "Mechanism for transforming growth factor beta and IL-2 enhancement of IgA expression in lipopolysaccharide-stimulated B cell cultures", J Immunol, 144, pp.952~959 (1990)
- McIntyre TM, "Transforming growth factor beta 1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide- activated murine B cells", J Exp Med, 177, pp.1031~1037 (1993)
- Kim HA, "TGF-beta1 and IFN-gamma stimulate mouse macrophages to express BAFF via different signaling pathways", J Leukoc Biol, 83, pp.1431~1439 (2008)
- Massagué J, "TGF-beta signal transduction", Annu Rev Biochem, 67, pp.753~791 (1998)
- Lebrun JJ, "Receptor serine kinases and signaling by activins and inhibins, In Inhibin, Activins and Flollistatin: regulatory functions in system and cell biology", pp.1~20 (1997), Springer-Verlag New York
- Shi Y, "Mechanisms of TGF-beta signaling from cell membrane to the nucleus", Cell, 113, pp.685~700 (2003)
- Lee HJ, "Activin A stimulates IgA expression in mouse B cells", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 366, pp.574~578 (2008), ACADEMIC PRESS INC ELSEVIER SCIENCE
- 박석래, "Smad3 and Smad4 mediate transforming growth factor-beta 1-induced IgA expression in murine B lymphocytes", EUROPEAN JOURNAL OF IMMUNOLOGY, 31, pp.1706~1715 (2001), WILEY-V C H VERLAG GMBH
- Moore PA, "BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator", Science, 285, pp.260~263 (1999)
- Nardelli B, "Synthesis and release of B-lymphocyte stimulator from myeloid cells", Blood, 97, pp.198~204 (2001)
- Chen YG, "Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis", Exp Biol Med (Maywood), 231, pp.534~544 (2006)
- Huang HM, "Basic fibroblast growth factor antagonizes activin A-mediated growth inhibition and hemoglobin synthesis in K562 cells by activating ERK1", 2 and deactivating p38 MAP kinase, 2004, pp.320, 1247~1252
- Ogihara T, "p38 MAPK is involved in activin A- and hepatocyte growth factor- mediated expression of pro-endocrine gene neurogenin 3 in AR42J-B13 cells", J Biol Chem, 278, pp.21693~21700 (2003)
- Zhang L, "MEKK1 transduces activin signals in keratinocytes to induce actin stress fiber formation and migration", Mol Cell Biol, 25, pp.60~65 (2005)
- Castigli E, "TACI and BAFF-R mediate isotype switching in B cells", J Exp Med, 201, pp.35~39 (2005)
- Yamada T, "B lymphocyte stimulator activates p38 mitogen-activated protein kinase in human Ig class switch recombination", Am J Respir Cell Mol Biol, 32, pp.388~394 (2005)
- 김현아, "Macrophage-derived BAFF induces AID expression through the p38MAPK", CREB and JNK, JOURNAL OF LEUKOCYTE BIOLOGY, pp.201103, 89(3)[DOI]