Enhancement of protease-induced IL-6 release in monocytic U-937 cells by phorbol-12-myristate-13-acetate.
OBJECTIVE
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.
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2+4, 14195 Berlin, Germany.
A
A
Domsalla
Matthias F
MF
Melzig
D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D010206:Papain / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*; D014357:Trypsin / Q000494:pharmacology*; D020298:U937 Cells
D015850:Interleukin-6; D014357:Trypsin; D013917:Thrombin; D010206:Papain; D013755:Tetradecanoylphorbol Acetate