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

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.