Tetracycline Derivatives Induce Apoptosis Selectively in Cultured Monocytes and Macrophages but not in Mesenchymal Cells
Tetracycline Derivatives Induce Apoptosis Selectively in Cultured Monocytes and Macrophages but not in Mesenchymal Cells
复制标题
四环素衍生物选择性诱导培养的单核细胞和巨噬细胞凋亡，但不诱导间充质细胞凋亡
作者：
J. Bettany;R. Wolowacz
提供了某些四环素衍生物表现出非抗生素活性的证据。该活性是对单核细胞谱系细胞（人组织细胞淋巴瘤U937细胞系和小鼠巨噬细胞系RAW264）的选择性细胞毒性，但对间充质谱系的各种细胞（包括原代绵羊关节软骨细胞和半月板细胞、鼠颅骨成骨细胞和MG-63骨肉瘤细胞以及原代人新生儿包皮成纤维细胞）没有选择性细胞毒性。在含血清和无血清培养条件下，将细胞与各种化学修饰的四环素衍生物 (CMT) 或多西环素以 0 至 50 μg/mL 之间的浓度范围孵育 24 小时。通过MTT测定对细胞活力的评估表明，化合物CMT-3诱导出有效的剂量依赖性细胞毒性作用，强力霉素诱导出较弱的作用，但在CMT-2或CMT-5存在的情况下没有明显的细胞毒性作用。通过 DNA 片段标记分析的细胞离心涂片制剂显示了相同的趋势，并表明细胞死亡是通过细胞凋亡机制实现的。这些四环素对单核细胞谱系细胞的细胞毒性效力可能会减弱，但不会因培养基中存在 10% 胎牛血清或用佛波酯预处理以促进更像巨噬细胞的表型而消除。这些数据提供的证据表明，除了充分表征的抗生素和 MMP 抑制特性之外，四环素可能通过一种新的机制发挥作用，诱导选择性细胞凋亡。
Evidence for a non-antibiotic activity displayed by certain tetracycline derivatives is presented. This activity is a selective cytotoxicity toward cells of the monocytic lineage (the human histiocytic lymphoma U937 cell line and the mouse macrophage line RAW264) but not toward various cells of a mesenchymal lineage (including primary ovine articular chondrocytes and meniscal cells, murine calvarial osteoblasts and MG-63 osteosarcoma cells, and primary human neonatal foreskin fibroblasts). Cells were incubated with various chemically modified tetracycline derivatives (CMTs) or doxycycline for 24 hrs at a range of concentrations between zero and 50 μg/mL in both serum-containing and serum-free culture conditions. Assessment of cell viability by means of the MTT assay demonstrated a potent dose-dependent cytotoxic effect induced by compound CMT-3 and a less potent effect induced by doxycycline, but no apparent cytotoxic effect in the presence of either CMT-2 or CMT-5. Cytospin preparations analyzed by the labeling of DNA fragments indicated the same trends and suggested that cell death was via an apoptotic mechanism. The cytotoxic potency of these tetracyclines toward cells of the monocytic lineage could be diminished but not abolished by either the presence of 10% fetal calf serum within the culture medium, or pre-treatment with phorbol esters to promote a more macrophage-like phenotype. These data provide evidence that, in addition to well-characterized antibiotic and MMPinhibitory characteristics, tetracyclines may function by a novel mechanism to induce selective apoptosis.
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影响因子：
37.8
作者：
P. Shah;E. Falk;J. Badimón;A. Fernández-Ortiz;A. Mailhac;G. Villareal-Levy;J. Fallon;J. Regnstrom;V. Fuster
通讯作者：
P. Shah;E. Falk;J. Badimón;A. Fernández-Ortiz;A. Mailhac;G. Villareal-Levy;J. Fallon;J. Regnstrom;V. Fuster
化学修饰的四环素抑制培养的大鼠系膜细胞中诱导型一氧化氮合酶的表达和一氧化氮的产生。
DOI：
10.1006/bbrc.1996.1787
发表时间：
1996
期刊：
Biochemical and biophysical research communications.
影响因子：
--
作者：
Trachtman,H;Futterweit,S;Greenwald,R;Moak,S;Singhal,P;Franki,N;Amin,AR
通讯作者：
Amin,AR
影响因子：
4.9
作者：
GLETTE, J;SANDBERG, S;SOLBERG, CO
通讯作者：
SOLBERG, CO
影响因子：
4.3
作者：
Petrinec, D;Liao, SX;Thompson, RW
通讯作者：
Thompson, RW
影响因子：
3.5
作者：
GOLUB, LM;LEE, HM;RAMAMURTHY, NS
通讯作者：
RAMAMURTHY, NS