Regulation of 92-kD gelatinase release in HL-60 leukemia cells: tumor necrosis factor-alpha as an autocrine stimulus for basal- and phorbol ester-induced secretion.
Regulation of 92-kD gelatinase release in HL-60 leukemia cells: tumor necrosis factor-alpha as an autocrine stimulus for basal- and phorbol ester-induced secretion.
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HL-60 白血病细胞中 92-kD 明胶酶释放的调节：肿瘤坏死因子-α 作为基础酯和佛波醇酯诱导分泌的自分泌刺激物。
作者：
Christian Ries;Helmut J. Kolb;Petro E. Petrides
基质金属蛋白酶9（MMP-9），也称为92-kD IV型胶原酶/明胶酶，被认为在肿瘤侵袭和转移中起关键作用。在这里，我们报告了通过酶谱分析确定的人早幼粒细胞细胞系HL-60中组成性释放的MMP-9。肿瘤坏死因子-α（TNF-α）增强酶释放三倍至四倍，蛋白激酶C（PKC）激活剂和分化诱导剂12-O-十四烷酰佛波醇-13-乙酸酯（TPA）八倍至九倍。明胶酶诱导TNF-α和TPA抑制放线菌素D或放线菌酮，表明从头蛋白质合成是必需的。中和TNF-α的单克隆抗体（抗TNF-α）降低了这些细胞的基础MMP-9释放。此外，这些抗体还显著干扰TPA诱导的酶释放。在HL-60细胞中抑制TNF-α表达的药物，如喷替茶碱和地塞米松，完全消除了组成性和TPA诱导的MMP-9释放。二乙基二硫代氨基甲酸酯，这是已知的刺激TNF-α的生产在HL-60细胞中，发挥了积极的作用，MMP-9的释放在未经处理的细胞，但抑制TPA处理的HL-60细胞。低浓度（100 ng/mL）的PKC抑制剂星形孢菌素导致未处理的培养物中MMP-9释放的显著增加，其通过添加抗TNF-α而被阻断。高浓度（2 μ mol/L）的星形孢菌素完全取消在未经处理的和TPA刺激的细胞的胞外酶活性。这些结果表明，在HL-60白血病细胞中，TNF-α是基础和PKC介导的MMP-9释放所必需的。因此，MMP-9的分泌可能不仅以旁分泌方式而且以自分泌方式受到TNF-α的调节。这可能增强未成熟白血病细胞在骨髓排出过程中的基质降解能力，并使这些细胞逃逸到外周组织中。
Matrix metalloproteinase 9 (MMP-9), also known as 92-kD type IV collagenase/gelatinase, is believed to play a critical role in tumor invasion and metastasis. Here, we report that MMP-9 was constitutively released from the human promyelocytic cell line HL-60 as determined by zymographic analysis. Tumor necrosis factor-alpha (TNF-alpha) enhanced the enzyme release threefold to fourfold and the protein kinase C (PKC) activator and differentiation inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) eightfold to ninefold. Gelatinase induction by TNF-alpha and TPA was inhibited by actinomycin D or cycloheximide, indicating that de novo protein synthesis was required. Neutralizing monoclonal antibodies to TNF-alpha (anti-TNF-alpha) decreased the basal MMP-9 release of these cells. In addition, these antibodies also significantly interfered with the TPA-induced enzyme release. Agents that inhibit TNF-alpha expression in HL-60 cells, such as pentoxifylline and dexamethasone, completely abrogated both the constitutive and TPA-evoked MMP-9 release. Diethyldithiocarbamate, which is known to stimulate TNF-alpha production in HL-60 cells, exerted a positive effect on MMP-9 release in untreated cells but was inhibitory in TPA-treated HL-60 cells. The PKC inhibitor staurosporine at low concentrations (100 ng/mL) caused a significant augmentation of MMP-9 release in untreated cultures that was blocked by the addition of anti-TNF-alpha. High concentrations (2 mumol/L) of staurosporine completely abolished the extracellular enzyme activity both in untreated and TPA-stimulated cells. These results suggest, that TNF-alpha is required for basal and PKC-mediated MMP-9 release in HL-60 leukemia cells. Thus, MMP-9 secretion may be regulated by TNF-alpha not only in a paracrine but also in an autocrine fashion. This may potentiate the matrix degradative capacity of immature leukemic cells in the processes of bone marrow egress and the evasion of these cells into peripheral tissue.
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DOI：
10.1016/s0021-9258(18)98977-5
发表时间：
1991-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tuula Salo;J. Lyons;F. Rahemtulla;H. Birkedal-Hansen;Hannu Larjava
通讯作者：
Tuula Salo;J. Lyons;F. Rahemtulla;H. Birkedal-Hansen;Hannu Larjava
磷脂酶 A2 激活和肿瘤坏死因子自诱导肿瘤坏死因子基因表达。
影响因子：
11.2
作者：
Spriggs,DR;Sherman,ML;Imamura,K;Mohri,M;Rodriguez,C;Robbins,G;Kufe,DW
通讯作者：
Kufe,DW
影响因子：
158.5
作者：
WEIDNER, N;SEMPLE, JP;FOLKMAN, J
通讯作者：
FOLKMAN, J
通过原位杂交证明急性成髓细胞白血病细胞中白细胞介素 1 β 转录本。
影响因子：
11.4
作者：
Nakamura,M;Kanakura,Y;Furukawa,Y;Ernst,TJ;Griffin,JD
通讯作者：
Griffin,JD
影响因子：
1.1
作者：
Lowery, Emily W.;Schneider, Susan M.
通讯作者：
Schneider, Susan M.