Role of NF-kB in glomerulonephritis

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Activation of the transcription factor NF-κB plays a pivotal role in inflammatory diseases by regulation of key mediators such as cytokines and chemokines. The central kinases in the multistep activation process of NF-κB are IKK2 (or IKKβ) and IKK1 (or IKKα). These kinases are therefore promising targets for pharmacological inhibition of NF-κB activation. IKK1 and IKK2 are dynamically activated and inactivated in the course of inflammation. Furthermore, they are differentially regulated in a cell lineage-specific manner. This project will concentrate on the analysis of cell-specific and time-dependent activation of NF-κB by IKK1 and IKK2 in an experimental model of crescentic glomerulonephritis. Understanding of the mechanisms that are relevant in differential activation of NF-κB in cell lineage specific leukocytes as well as in resident renal cells might be of great importance for future therapeutic strategies in patients with rapidly progressive glomerulonephritis.