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.
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.
Park
Sun-Mi
SM
Department of Biology and Protein Network Research Center, Yonsei University, Seoul, Korea.
Kim
Sunshin
S
Choi
Jin-Suk
JS
Hur
Dae-Young
DY
Lee
Wang-Jae
WJ
Lee
Myung-Shik
MS
Choe
Jongseon
J
Lee
Tae H
TH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017209:Apoptosis / Q000276:immunology*; D016466:CHO Cells; D053181:Caspase 8; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis; D016923:Cell Death / Q000276:immunology; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D053222:Fas Ligand Protein; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012995:Solubility; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology
D000911:Antibodies, Monoclonal; D061945:Caspase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C505530:CASP8 protein, human; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases