Startseite Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
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Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis

  • Hyesook Yoon und Isobel A. Scarisbrick EMAIL logo
Veröffentlicht/Copyright: 17. August 2016

Abstract

Kallikrein-related peptidase 6 (Klk6) is elevated in the serum of multiple sclerosis (MS) patients and is hypothesized to participate in inflammatory and neuropathogenic aspects of the disease. To test this hypothesis, we investigated the impact of systemic administration of recombinant Klk6 on the development and progression of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). First, we determined that Klk6 expression is elevated in the spinal cord of mice with EAE at the peak of clinical disease and in immune cells upon priming with the disease-initiating peptide in vitro. Systemic administration of recombinant Klk6 to mice during the priming phase of disease resulted in an exacerbation of clinical symptoms, including earlier onset of disease and higher levels of spinal cord inflammation and pathology. Treatment of MOG35-55-primed immune cells with Klk6 in culture enhanced expression of pro-inflammatory cytokines, interferon-γ, tumor necrosis factor, and interleukin-17, while reducing anti-inflammatory cytokines interleukin-4 and interleukin-5. Together these findings provide evidence that elevations in systemic Klk6 can bias the immune system towards pro-inflammatory responses capable of exacerbating the development of neuroinflammation and paralytic neurological deficits. We suggest that Klk6 represents an important target for conditions in which pro-inflammatory responses play a critical role in disease development, including MS.

Award Identifier / Grant number: 5R01NS052741

Funding statement: Studies were supported by the National Institutes of Health 5R01NS052741, RG4958 from the National Multiple Sclerosis Society to I.A.S. The authors declare no competing financial interests.

Acknowledgments

Studies were supported by the National Institutes of Health 5R01NS052741, RG4958 from the National Multiple Sclerosis Society to I.A.S. The authors declare no competing financial interests.

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Received: 2016-6-20
Accepted: 2016-8-10
Published Online: 2016-8-17
Published in Print: 2016-12-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: remodelling the KLK landscape down under
  4. HIGHLIGHT: 6TH INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
  5. Kallikrein(K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications
  6. Mechanistic insight from murine models of Netherton syndrome
  7. Development of molecules stimulating the activity of KLK3 – an update
  8. Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors
  9. Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10
  10. Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer
  11. Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
  12. A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene
  13. Therapeutic modulation of tissue kallikrein expression
  14. In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B
  15. A computational analysis of the genetic and transcript diversity at the kallikrein locus
  16. Reviews
  17. Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome
  18. The power, pitfalls and potential of the nanodisc system for NMR-based studies
  19. Research Articles/Short Communications
  20. Cell Biology and Signaling
  21. Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1β and 5-azacytidine
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