Effects of serine protease inhibitor, TAME, on IL-1 beta in LPS-stimulated human monocytes: relationship between synthesis and release of a 33-kDa precursor and the 17-kDa biologically active species.
In: Inflammation, Jg. 17 (1993-10-01), Heft 5, S. 613-31
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Zugriff:
LPS stimulation of human monocytes in vitro induced release of the 17-kDa mature IL-1 beta (mIL-1 beta) but did not result in release of precursor IL-1 beta (pIL-1 beta). In contrast, the presence of a serine protease inhibitor, N alpha-(p-toluene sulfonyl)-L-arginine methyl ester (TAME; 10 mM) for 6 or 18 h was associated with the LPS-stimulated release of the 33-kDa pIL-1 beta as well. These effects were initially discerned from observations that the fraction of the total IL-1 beta produced (as detected by ELISA) that was released from monocytes increased in the presence of TAME, and immunoblot assays confirmed that this fraction was predominantly 33-kDa IL-1 beta. A global decrease in monocyte protein synthesis was also observed after prolonged (18-h) exposure to TAME and was associated with a decrease in IL-1 beta synthesis, predominantly affecting 31-kDa pIL-1 beta, and a dose-dependent inhibition of TNF-alpha production. Parallel examination of lactate dehydrogenase (LDH) release indicated that pIL-1 beta release was unrelated to cell lysis. These results demonstrate that TAME-inhibitable serine proteases are probably involved in the production and eventual proteolysis of the 33-kDa pIL-1 beta in situ but are probably not mechanistically related to either maturation of the IL-1 beta molecule or signaling of IL-1 beta release. IL-1 beta release appears to be dependent on the amount of total IL-1 beta synthesized. Serine proteolysis may constitute a degradative pathway for excess precursor, which, if interfered with, could result in release of the higher-molecular-weight forms of IL-1 beta.
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Effects of serine protease inhibitor, TAME, on IL-1 beta in LPS-stimulated human monocytes: relationship between synthesis and release of a 33-kDa precursor and the 17-kDa biologically active species.
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Autor/in / Beteiligte Person: | Jessop, JJ ; Henry, SL ; Hoffman, T |
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Zeitschrift: | Inflammation, Jg. 17 (1993-10-01), Heft 5, S. 613-31 |
Veröffentlichung: | 1999- : New York, NY : Kluwer Academic/Plenum Publishers ; <i>Original Publication</i>: New York, Plenum Press., 1993 |
Medientyp: | academicJournal |
ISSN: | 0360-3997 (print) |
DOI: | 10.1007/BF00914198 |
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