Tae H. Lee

Isolation and characterization of eight tumor necrosis factor-induced gene sequences from human fibroblasts.

A lambda cDNA library was prepared from polyadenylated RNA isolated from quiescent human diploid FS-4 fibroblasts stimulated with tumor necrosis factor for 3 h. Differential screening was used to isolate cDNA sequences that are stimulated by tumor necrosis factor. Eight distinct tumor necrosis factor-stimulated gene sequences (designated TSG-1, -6, -8, -12, -14, -21, -27, and -37) were partially sequenced and compared with known sequences from GenBank. TSG-1 was identical to the gene for interleukin-8. TSG-8 corresponded to the gene for monocyte chemotactic and activating factor. TSG-21 and -27 were identical to the genes for collagenase and stromelysin, respectively. The other four sequences showed no homologies with known genes. Patterns of induction of mRNAs corresponding to the eight cloned cDNAs by various cytokines, growth factors, and activators of second messenger pathways were analyzed in FS-4 cells.

TGF-β Inhibits Fas-Mediated Apoptosis of a Follicular Dendritic Cell Line by Down-Regulating the Expression of Fas and Caspase-8: Counteracting Role of TGF-β 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-β inhibits Fas-mediated apoptosis of HK cells by down-regulating the expression of surface Fas and caspase-8. The inhibitory effect of TGF-β can be observed when HK cells were simultaneously treated with TNF and TGF-β, indicating that TGF-β counteracts the effect of TNF in sensitizing cells to Fas-mediated apoptosis. Furthermore, the deprivation of TGF-β by injecting neutralizing TGF-β Abs to the SRBC-immunized mice resulted in the sporadic appearance of FDC undergoing apoptosis in the lymphoid follicles, suggesting that TGF-β functions as a naturally occurring inhibitor that rescues FDCs which are predisposed to apoptosis. Our study documents a novel function of TGF-β in the maintenance of FDC networks.