title: Evidence for a crucial role of neutrophil-derived serine proteases in the inactivation of interleukin-6 at sites of inflammation.
abstract: The bioactivity of interleukin-6 (IL-6) was found to be dramatically reduced in fluids from sites of inflammation. Here, we provide evidence that the neutrophil-derived serine proteases elastase, proteinase 3 and cathepsin G are mainly involved in its degradation and subsequent inactivation. The initially hydrolyzed peptide bonds were detected to be Val(11)-Ala(12) and Leu(19)-Thr(20) (elastase), Phe(78)-Asn(79) (cathepsin G) and Ala(145)-Ser(146) (proteinase 3). The soluble IL-6 receptor elicits a protective effect against the IL-6 inactivation by cathepsin G only. The inactivation of IL-6 by neutrophil-derived serine proteases might act as a feedback mechanism terminating the IL-6-induced activation of neutrophils.
authors.affiliation: Institute of Immunology, Center of Internal Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120, Magdeburg, Germany. ute.bank@medizin.uni-magdeburg.de
authors.forename: U
authors.initials: U
authors.lastname: Bank
authors.forename: B
authors.initials: B
authors.lastname: Küpper
authors.forename: D
authors.initials: D
authors.lastname: Reinhold
authors.forename: T
authors.initials: T
authors.lastname: Hoffmann
authors.forename: S
authors.initials: S
authors.lastname: Ansorge
mesh_terms: D056649:Cathepsin G; D002403:Cathepsins / Q000502:physiology*; D005122:Exudates and Transudates / Q000201:enzymology* / Q000276:immunology; D005246:Feedback; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis; D019272:Leukocyte Elastase / Q000502:physiology*; D053146:Myeloblastin; D009504:Neutrophils / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D056649:Cathepsin G; D002403:Cathepsins; D015850:Interleukin-6; D019272:Leukocyte Elastase; D053146:Myeloblastin; D012697:Serine Endopeptidases; D000093242:Interleukin-6 Inhibitors; C534094:CTSG protein, human