title: Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases.
abstract: In renal tissue injury, activation of the transcription factor NF-kappaB has a central role in the induction of proinflammatory gene expression, which are involved in the development of progressive renal inflammatory disease. The function of NF-kappaB during the switch from the inflammatory process toward resolution, however, is largely unknown. Therefore, we assessed the time-dependent activation and function of NF-kappaB in two different models of acute nephritis. Our experiments demonstrate a biphasic activation of NF-kappaB in the anti-Thy-1 model of glomerulonephritis in rats and the LPS-induced nephritis in mice, with a first peak during the induction phase and a second peak during the resolution period. After induction of glomerular immune injury in rats, predominantly NF-kappaB p65/p50 heterodimer complexes are shifted to the nucleus whereas during the resolution phase predominantly p50 homodimers could be demonstrated in the nuclear compartment. In addition, we could demonstrate that p50 protein plays a pivotal role in the resolution of LPS-induced renal inflammation since NF-kappaB p50 knockout mice demonstrate significantly higher chemokine expression, prolonged renal inflammatory cell infiltration with consecutive tissue injury, and reduced survival. In conclusion, our studies indicate that NF-kappaB subunit p50 proteins have critical in vivo functions in immunologically mediated renal disease by downregulating inflammation during the resolution period.
authors.affiliation: III. Medizinische Klinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.forename: Claudia
authors.initials: C
authors.lastname: von Ruffer
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Meyer
authors.forename: Gunther
authors.initials: G
authors.lastname: Zahner
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Guerrero
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Udo
authors.initials: U
authors.lastname: Helmchen
authors.forename: Gilbert W
authors.initials: GW
authors.lastname: Moeckel
authors.forename: Gunter
authors.initials: G
authors.lastname: Wolf
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Friedrich
authors.initials: F
authors.lastname: Thaiss
mesh_terms: D021581:Active Transport, Cell Nucleus; D000208:Acute Disease; D000818:Animals; D000961:Antilymphocyte Serum; D026501:Blotting, Southwestern; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055503:Protein Multimerization; D051381:Rats; D017208:Rats, Wistar; D012075:Remission, Spontaneous; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism
chemical_list: D000961:Antilymphocyte Serum; D018925:Chemokines; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; C498145:Rela protein, rat; C497595:Relb protein, rat; D051996:Transcription Factor RelA; C440499:lipopolysaccharide, Escherichia coli O111 B4; C073701:Nfkb1 protein, mouse; D051841:Transcription Factor RelB