Hyaluronidase enhancement of TNF-mediated cell death is reversed by TGF-β1

被引:23
作者
Chang, NS [1 ]
机构
[1] Guthrie Med Ctr, Guthrie Res Inst, Lab Mol Immunol, Sayre, PA 18840 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1997年 / 273卷 / 06期
关键词
transforming growth factor-beta 1; tumor necrosis factor; apoptosis; L929; cells; LNCaP cells;
D O I
10.1152/ajpcell.1997.273.6.C1987
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Both hyaluronidase and transforming growth factor (TGF)-beta 1 play a significant role in the development of prostate cancer. In this study, the regulation of tumor necrosis factor (TNF)-mediated cell death by hyaluronidase and TGF-beta 1 was investigated. Preexposure of L929 fibroblasts, prostate LNCaP cells, and epithelial My 1 Lu cells to hyaluronidase for a minimum of 12 h resulted in significant enhancement of cell death by TNF. Phosphorylation of p42 and p44 mitogen-activated protein (MAP) kinases was found by stimulation of L929 cells with hyaluronidase for 30 min, indicating that the Raf/MAP kinase-extracellular signal-regulating protein kinase (MEK)/ MAP kinase pathway was activated. However, blocking the activation of upstream MAP kinase kinase (MEK 1 and 2 kinase) by PD-98059 failed to inhibit the hyaluronidase-enhanced TNF killing of cells, suggesting that hyaluronidase-mediated degradation of extracellular matrix and membrane components may elicit multiple signaling pathways. As a potent stimulator of extracellular matrix protein synthesis, TGF-beta 1 blocked the hyaluronidase-enhanced death of L929 and LNCaP cells mediated by TNF. TGF-beta 1 activated protein-tyrosine kinases in L929 cells, in which the tyrosine kinase inhibitors lavendustin A and tyrphostin blocked the activation as well as the TGF-beta 1 inhibition of hyaluronidase effects. Functional antagonism was also observed between hyaluronidase and TGF-beta 1 in cell growth regulation. For example, TGF-pl-mediated suppression of epithelial My 1 Lu cell growth was abolished by hyaluronidase. Overall, it is demonstrated in this study that hyaluronidase reciprocally antagonized TGF-beta 1 in the modulation of cell proliferation and TNF-mediated death.
引用
收藏
页码:C1987 / C1994
页数:8
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