A Domsalla1, Matthias F Melzig. 1. Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2+4, 14195 Berlin, Germany.
Abstract
OBJECTIVE AND DESIGN: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These findings suggest a synergistic activity between phorbol ester and proteases to promote inflammation.
OBJECTIVE AND DESIGN: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: These findings suggest a synergistic activity between phorbol ester and proteases to promote inflammation.
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