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Enhancement of protease-induced IL-6 release in monocytic U-937 cells by phorbol-12-myristate-13-acetate

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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.

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Correspondence to Matthias F. Melzig.

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Responsible Editor: Graham Wallace.

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Domsalla, A., Melzig, M.F. Enhancement of protease-induced IL-6 release in monocytic U-937 cells by phorbol-12-myristate-13-acetate. Inflamm. Res. 61, 1125–1129 (2012). https://doi.org/10.1007/s00011-012-0505-z

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  • DOI: https://doi.org/10.1007/s00011-012-0505-z

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