The role of NF-kB in an animal model of ANCA-associated vasculitis and therapeutic options using NF-kB inhibition

• Applicant: Privatdozentin Dr. Mira Choi
• Subject Area: Nephrology ; Immunology
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243570026

Antineutrophil cytoplasmic antibodies (ANCA) activate neutrophils leading to endothelial cell damage which plays a crucial role in the pathogenesis of vasculitis and glomerulonephritis. Therapeutic options using corticosteroids and cytotoxic immunosuppressive agents reduce mortality, but have a lot of side effects. A deeper insight into disease development and new therapeutic strategies is needed. We will test the hypothesis that NF-kB mediates necrotizing vessel inflammation in ANCA-associated vasculitis. We will 1) investigate NF-kB activity in a mouse model of anti-MPO NCGN (necrotizing and crescentic glomerulonephritis) and in human kidney biopsies from patients with ANCA-associated vasculitis, including the definition of mainly involved cell types. 2) Preliminary experiments suggest that endothelial cells play an important role mediating NF-kB induction and disease development. We will perform in vitro experiments with ANCA-activated neutrophils and endothelial cells. Furthermore we will 3) use NF-kB deficient mice models to elucidate the impact of NF-kB for induction and development of ANCA-induced vasculitis and 4) will test therapeutic options in anti-MPO NCGN using specific NF-kB inhibitors.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Claus Scheidereit