Sneaking-ligand fusion proteins attenuate serum transfer arthritis by endothelium-targeted NF-κB inhibition.
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.
Department of Rheumatology and Clinical Immunology and Centre of Chronic Immunodeficiency, University Medical Centre and University of Freiburg, Hugstetter Street 55, 79106, Freiburg, Germany, Bettina.Sehnert@uniklinik-freiburg.de.
Bettina
B
Sehnert
Harald
H
Burkhardt
Michael J
MJ
May
Jochen
J
Zwerina
Reinhard E
RE
Voll
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage
D008024:Ligands; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins