Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2+4, 14195 Berlin, Germany.
Inflamm Res. 2012 Oct;61(10):1125-9. doi: 10.1007/s00011-012-0505-z. Epub 2012 Jun 14.
Serine proteases and phorbol-12-myristate-13-acetate (PMA) are able to induce the release of pro-inflammatory interleukin-6 (IL-6) in monocytic cells. The present study was performed to investigate whether there is any interaction between proteases and phorbol ester in IL-6 release.
U-937 cells differentiated with interferon-γ were treated with or without thrombin, trypsin, papain (each 1-10 μg/ml) and PMA (0.1-10 ng/ml) or the combination of both enzyme and PMA for up to 72 h and the release of IL-6 was determined by enzyme-linked immunosorbent assay.
Thrombin and PMA caused a time- and dose-dependent increase in IL-6. The combination of the two resulted in an increase up to fivefold higher than each agent alone. Even the combination of the cysteine protease papain and PMA showed a strong effect on IL-6 release compared to the individual tests.
These findings suggest a synergistic activity between phorbol ester and proteases to promote inflammation.
丝氨酸蛋白酶和佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）能够诱导单核细胞释放促炎细胞因子白细胞介素 6（IL-6）。本研究旨在探讨蛋白酶和佛波酯在 IL-6 释放中的相互作用。
用干扰素-γ诱导分化的 U-937 细胞用或不用凝血酶、胰蛋白酶、木瓜蛋白酶（各 1-10μg/ml）和 PMA（0.1-10ng/ml）或两者的组合处理，最长达 72 小时，并通过酶联免疫吸附试验测定 IL-6 的释放。
凝血酶和 PMA 导致 IL-6 的时间和剂量依赖性增加。两者的组合导致增加了五倍以上，比单独使用每种药物都要高。即使是半胱氨酸蛋白酶木瓜蛋白酶和 PMA 的组合与单独测试相比，对 IL-6 释放也表现出很强的作用。
这些发现表明佛波醇酯和蛋白酶之间存在协同作用，以促进炎症。
