Inactivation of interleukin-6 by neutrophil proteases at sites of inflammation. Protective effects of soluble IL-6 receptor chains.
In contrast to the excessively elevated immunochemically detectable concentrations of interleukin-6 (IL-6) in inflammatory exudates, the IL-6 bioactivities are significantly reduced, suggesting an inactivation of IL-6 at sites of inflammation. Since high amounts of proteases are released by invading neutrophils (PMN) in close temporal correlation to elevated IL-6 concentrations at sites of inflammation, this study focused on effects of the PMN-derived proteases elastase (NE), proteinase 3 (PR 3) and cathepsin G (Cat G) on the bioactivity and molecular integrity of IL-6. Here, we demonstrate that these enzymes play a crucial role in the initiation of the degradation and subsequent inactivation of IL-6 at sites of inflammation. Soluble IL-6 receptor subunits elicit a protective effect against the IL-6 inactivation by Cat G, only. Possible consequences of the proteolytical IL-6 inactivation for local inflammatory processes will be discussed.
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Institute of Immunology, Otto-von-Guericke-Universität, Magdeburg.
Küpper
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Ansorge
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D000208:Acute Disease; D001202:Ascitic Fluid / Q000201:enzymology; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D002474:Cell-Free System; D005122:Exudates and Transudates / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D015850:Interleukin-6 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism*; D053146:Myeloblastin; D009504:Neutrophils / Q000201:enzymology*; D010996:Pleural Effusion / Q000201:enzymology; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D012995:Solubility; D013582:Synovial Fluid / Q000201:enzymology; D000093242:Interleukin-6 Inhibitors
D056649:Cathepsin G; D002403:Cathepsins; D015850:Interleukin-6; D019272:Leukocyte Elastase; D053146:Myeloblastin; D019947:Receptors, Interleukin-6; D012697:Serine Endopeptidases; D000093242:Interleukin-6 Inhibitors; C534094:CTSG protein, human