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: U Bank, B Küpper, D Reinhold, T Hoffmann, S Ansorge
• Journal: FEBS letters (FEBS Lett) Vol. 461 Issue 3 Pg. 235-40 (Nov 19 1999) ISSN: 0014-5793 [Print] England
• PMID: 10567703 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Interleukin-6
• Cathepsins
• Serine Endopeptidases
• CTSG protein, human
• Cathepsin G
• Leukocyte Elastase
• Myeloblastin

Topics

• Cathepsin G
• Cathepsins (physiology)
• Exudates and Transudates (enzymology, immunology)
• Feedback
• Humans
• Inflammation (enzymology, immunology)
• Interleukin-6 (analysis, antagonists & inhibitors)
• Leukocyte Elastase (physiology)
• Myeloblastin
• Neutrophils (enzymology)
• Serine Endopeptidases (physiology)