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TGF-beta inhibits Fas-mediated apoptosis of a follicular dendritic cell line by down-regulating the expression of Fas and caspase-8: counteracting role of TGF-beta on TNF sensitization of Fas-mediated apoptosis

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Authors
Park, Sun-Mi; Kim, Sungshin; Choi, Jin-Suk; Hur, Dae-Young; Lee, Wang-Jae; Lee, Myung-Shik; Choe, Jongseon; Lee, Tae H.
Issue Date
2005-05-10
Publisher
American Association of Immunologists
Citation
J Immunol. 2005 May 15;174(10):6169-75.
Keywords
AnimalsAntibodies, Monoclonal/administration & dosageAntigens, CD95/biosynthesis/*metabolism/physiologyApoptosis/*immunologyCHO CellsCaspase 8Caspases/*antagonists & inhibitors/biosynthesisCell Death/immunologyCell Membrane/enzymology/immunology/metabolismCells, CulturedCricetinaeDendritic Cells, Follicular/cytology/*immunology/metabolismDown-Regulation/*immunologyFas Ligand ProteinGerminal Center/cytology/immunologyGrowth Inhibitors/antagonists & inhibitors/immunology/*physiologyHumansMembrane Glycoproteins/physiologyMiceMice, Inbred C57BLMice, NudeSolubilityTransforming Growth Factor beta/antagonists &inhibitors/immunology/*physiologyTumor Necrosis Factor-alpha/*antagonists & inhibitors/physiology
Abstract
Follicular dendritic cells (FDC) constitute the framework of germinal center (GC) in secondary lymphoid follicles, and the integrity of FDC networks is critically affected by cytokines present in the GC. We have previously shown that TNF promotes Fas-mediated apoptosis of HK cells, an established FDC-like cell line, by up-regulating Fas expression. However, in the developing GC, FDC death is not a hallmark of GC despite the presence of TNF and FasL. In this study, we report that TGF-beta inhibits Fas-mediated apoptosis of HK cells by down-regulating the expression of surface Fas and caspase-8. The inhibitory effect of TGF-beta can be observed when HK cells were simultaneously treated with TNF and TGF-beta, indicating that TGF-beta counteracts the effect of TNF in sensitizing cells to Fas-mediated apoptosis. Furthermore, the deprivation of TGF-beta by injecting neutralizing TGF-beta Abs to the SRBC-immunized mice resulted in the sporadic appearance of FDC undergoing apoptosis in the lymphoid follicles, suggesting that TGF-beta functions as a naturally occurring inhibitor that rescues FDCs which are predisposed to apoptosis. Our study documents a novel function of TGF-beta in the maintenance of FDC networks.
ISSN
0022-1767 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15879113

http://hdl.handle.net/10371/29495
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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