|Titel:||Role for NF-κB1 (p50) in an experimental model of rapid progressive glomerulonephritis||Sonstige Titel:||Rolle von NF-κB1 (p50) in einem experimentellen Modell der Rapid Progressiven Glomerulonephritis||Sprache:||Englisch||Autor*in:||Nauroz, Martin||Schlagwörter:||glomerulonephritis; nfkb; p50; niere; glomerulonephritis; nfkb; p50; kidney||Erscheinungsdatum:||2013||Tag der mündlichen Prüfung:||2013-11-18||Zusammenfassung:||
Rapid progressive glomerulonephritis is one of the main causes for end-stage renal disease. The fundamental characteristic and morphological hallmark of glomerular inflammatory lesions are infiltrating macrophages and T-cells into the kidney. These cells produce cytokines and attract other immune cells by the secretion of chemokines which promotes glomerular tissue injury and damage. Therapeutic strategies so far are toxic and unspecific and therefore specific therapies with fewer side effects are needed.
In renal tissue injury activation of the transcription factor NF-κB plays a pivotal role in the induction of proinflammatory gene expression, which is involved in the development of progressive renal inflammatory disease. The function of NF-κB during the switch from the inflammatory process toward resolution, however, is largely unknown. NF-κB acts as a pro-inflammatory as well as an anti-inflammatory transcription factor depending on its subunit composition. NF-κB subunit Nfkb1 (p50) or rather p50/p50-homodimers play a decisive role during the switch to resolution of inflammation. This thesis therefore analyzes the time-dependent activation and function of NF-κB in wild type as well as in Nfkb1-/- mice in a model of experimental nephrotoxic nephritis (NTN).
After induction of nephrotoxic serum nephritis both strains of mice developed a nephritic syndrome and inflammatory renal disease with reduced renal function and severe renal damage during the 21 days observation period. Renal damage was accompanied by an infiltration of CD3+-T- and F4/80+-cells. When compared to wild type mice, mice lacking Nfkb1 had a much higher pro-inflammatory cytokine and chemokine expression and a higher mortality rate. Therefore, Nfkb1 is essential to limit inflammation and tissue damage by reducing cytokine and chemokine expression after NTN induction. As activation of NF-κB was oscillatory after induction of disease Nfkb1 and p50/p50-homodimers in wild type mice was associated with better renal function, reduced renal damage, less infiltrating inflammatory cells and reduced cytokine expression.
Therefore, Nfkb1 plays a critical role to limit tissue damage and cytokine expression after induction of an acute inflammatory glomerular disease. It seems obvious that resolution of inflammation is an active process and Nfkb1 has a critical role during this process.
|URL:||https://ediss.sub.uni-hamburg.de/handle/ediss/5236||URN:||urn:nbn:de:gbv:18-65485||Dokumenttyp:||Dissertation||Betreuer*in:||Thaiss, Friedrich (Prof. Dr.)|
|Enthalten in den Sammlungen:||Elektronische Dissertationen und Habilitationen|