Advanced search
1 file | 198.45 KB Add to list

The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages stimulated by lipopolysaccharide

(2001) JOURNAL OF BIOLOGICAL CHEMISTRY. 276(24). p.21153-21157
Author
Organization
Abstract
Cathepsin B has previously been shown to proteolytically activate the proinflammatory caspase-11 in vitro, Here we show that cathepsin B is not involved in activation of caspase-11 induced by lipopolysaccharide (LPS) and subsequent maturation of interleukin (IL)-1 beta in macrophages. Nevertheless, we found that the cathepsin B inhibitor benzyloxycarbonyl-Phe-Ala-fluoromethylketone (z-FA.fmk) prevents LPS-induced production of IL-1 alpha, IL-1 beta, and tumor necrosis factor at the transcriptional level. The latter was not because of cathepsin B inhibition, but was mediated by inhibition of the transactivation potential of the nuclear factor kappaB (NF-kappaB). z-FA.fmk did not prevent LPS-induced activation of p38 mitogen-activated protein kinase, which was shown to be involved in NF-kappaB transactivation in response to LPS. These results suggest that the previously described therapeutic effect of z-FA.fmk in the treatment of rheumatoid arthritis might not only result from inhibition of cathepsin B but also implicates an important contribution from the inhibition of NF-kappaB-dependent gene expression.
Keywords
TUMOR-NECROSIS-FACTOR, NF-KAPPA-B, PEPTIDYL FLUOROMETHYL KETONES, RHEUMATOID-ARTHRITIS, TRANSCRIPTION FACTOR, DEPENDENT TRANSCRIPTION, ALPHA DEGRADATION, GENE-EXPRESSION, ACTIVATION, CELLS

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 198.45 KB

Citation

Please use this url to cite or link to this publication:

MLA
Schotte, Peter, Reinout Schauvliege, Sophie Janssens, et al. “The Cathepsin B Inhibitor z-FA.fmk Inhibits Cytokine Production in Macrophages Stimulated by Lipopolysaccharide.” JOURNAL OF BIOLOGICAL CHEMISTRY 276.24 (2001): 21153–21157. Print.
APA
Schotte, P., Schauvliege, R., Janssens, S., & Beyaert, R. (2001). The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages stimulated by lipopolysaccharide. JOURNAL OF BIOLOGICAL CHEMISTRY, 276(24), 21153–21157.
Chicago author-date
Schotte, Peter, Reinout Schauvliege, Sophie Janssens, and Rudi Beyaert. 2001. “The Cathepsin B Inhibitor z-FA.fmk Inhibits Cytokine Production in Macrophages Stimulated by Lipopolysaccharide.” Journal of Biological Chemistry 276 (24): 21153–21157.
Chicago author-date (all authors)
Schotte, Peter, Reinout Schauvliege, Sophie Janssens, and Rudi Beyaert. 2001. “The Cathepsin B Inhibitor z-FA.fmk Inhibits Cytokine Production in Macrophages Stimulated by Lipopolysaccharide.” Journal of Biological Chemistry 276 (24): 21153–21157.
Vancouver
1.
Schotte P, Schauvliege R, Janssens S, Beyaert R. The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages stimulated by lipopolysaccharide. JOURNAL OF BIOLOGICAL CHEMISTRY. 2001;276(24):21153–7.
IEEE
[1]
P. Schotte, R. Schauvliege, S. Janssens, and R. Beyaert, “The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages stimulated by lipopolysaccharide,” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 24, pp. 21153–21157, 2001.
@article{140083,
  abstract     = {Cathepsin B has previously been shown to proteolytically activate the proinflammatory caspase-11 in vitro, Here we show that cathepsin B is not involved in activation of caspase-11 induced by lipopolysaccharide (LPS) and subsequent maturation of interleukin (IL)-1 beta in macrophages. Nevertheless, we found that the cathepsin B inhibitor benzyloxycarbonyl-Phe-Ala-fluoromethylketone (z-FA.fmk) prevents LPS-induced production of IL-1 alpha, IL-1 beta, and tumor necrosis factor at the transcriptional level. The latter was not because of cathepsin B inhibition, but was mediated by inhibition of the transactivation potential of the nuclear factor kappaB (NF-kappaB). z-FA.fmk did not prevent LPS-induced activation of p38 mitogen-activated protein kinase, which was shown to be involved in NF-kappaB transactivation in response to LPS. These results suggest that the previously described therapeutic effect of z-FA.fmk in the treatment of rheumatoid arthritis might not only result from inhibition of cathepsin B but also implicates an important contribution from the inhibition of NF-kappaB-dependent gene expression.},
  author       = {Schotte, Peter and Schauvliege, Reinout and Janssens, Sophie and Beyaert, Rudi},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keywords     = {TUMOR-NECROSIS-FACTOR,NF-KAPPA-B,PEPTIDYL FLUOROMETHYL KETONES,RHEUMATOID-ARTHRITIS,TRANSCRIPTION FACTOR,DEPENDENT TRANSCRIPTION,ALPHA DEGRADATION,GENE-EXPRESSION,ACTIVATION,CELLS},
  language     = {eng},
  number       = {24},
  pages        = {21153--21157},
  title        = {The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages stimulated by lipopolysaccharide},
  url          = {http://dx.doi.org/10.1074/jbc.M102239200},
  volume       = {276},
  year         = {2001},
}

Altmetric
View in Altmetric
Web of Science
Times cited: