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NF-kappa B pp 579-591 | Cite as

Sneaking-Ligand Fusion Proteins Attenuate Serum Transfer Arthritis by Endothelium-Targeted NF-κB Inhibition

  • Bettina Sehnert
  • Harald Burkhardt
  • Michael J. May
  • Jochen Zwerina
  • Reinhard E. Voll
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1280)

Abstract

The nuclear transcription factor κB (NF-κB) is a crucial mediator of the inflammatory and immune response. The contribution of dysregulated NF-κB is established in the pathogenesis of arthritis. Accordingly, NF-κB represents an attractive molecular target for the development of therapeutic interventions in inflammatory diseases. However, ubiquitous pharmacologic suppression of NF-κB activity is limited by the hazards of toxic side effects and profound immunosuppression. Cell type-specific NF-κB inhibition with the “sneaking-ligand” approach could identify disease-relevant cell types and improve risk-benefit ratios of therapeutic interventions. Vascular endothelial cells act as a gatekeeper and are crucial for leukocyte recruitment into sites of inflammation. The endothelium-specific NF-κB inhibitor SLC1 ameliorates serum transfer arthritis in mice and protects against inflammation and cartilage destruction. In this chapter, we describe the SLC1 treatment schedule in the K/BxN serum transfer arthritis and present the evaluation system to analyze arthritis severity and histopathological alterations.

Key words

NF-κB Endothelium Sneaking-ligand approach Mouse model Arthritis 

Notes

Acknowledgments

The work in the author’s laboratory was supported by the German Research Foundation (SFB 643 project B3 and A8; FOR 832, project 7; Sachbeihilfe DU337/3-2 and BU 584/4-1), BMBF 01EO0803 Grant to the Centre of Chronic Immunodeficiency, the Federal State of Hessen (LOEWE-Project: Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University Frankfurt), the German Federal Ministry of Education and Research ArthroMark (project 4, 01 EC 1009C), and National Institutes of Health/National Heart, Lung, and Blood Institute Grant RO1HL096642.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Bettina Sehnert
    • 1
  • Harald Burkhardt
    • 2
  • Michael J. May
    • 3
  • Jochen Zwerina
    • 4
  • Reinhard E. Voll
    • 1
  1. 1.Department of Rheumatology and Clinical Immunology and Centre of Chronic ImmunodeficiencyUniversity Medical Centre and University of FreiburgFreiburgGermany
  2. 2.Division of Rheumatology, Department of Internal Medicine II and Fraunhofer IME-Project-Group Translational Medicine and PharmacologyJohann Wolfgang Goethe University Frankfurt am MainFrankfurt am MainGermany
  3. 3.School of Veterinary MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Internal Medicine 3University of Erlangen-NürnbergErlangenGermany

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