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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/F429    most recent 90435.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Panzer, U. Articles by Thaiss, F. PubMed PubMed Citation Articles by Panzer, U. Articles by Thaiss, F.

Resolution of renal inflammation: a new role for NF-B1 (p50) in inflammatory kidney diseases

¹III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf; ²Renal Research Laboratory, Fundación Jiménez Díaz, Autonoma University, Madrid, Spain; ³TU Universitätsklinikum, München, Germany; ⁴Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; ⁵Department of Pathology Vanderbilt University, Nashville, Tennessee; and ⁶Klinik für Innere Medizin III, Klinikum der Friedrich-Schiller-Universität, Jena, Germany

Submitted 23 July 2008 ; accepted in final form 15 May 2009

In renal tissue injury, activation of the transcription factor NF-B 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-B during the switch from the inflammatory process toward resolution, however, is largely unknown. Therefore, we assessed the time-dependent activation and function of NF-B in two different models of acute nephritis. Our experiments demonstrate a biphasic activation of NF-B 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-B 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-B 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-B subunit p50 proteins have critical in vivo functions in immunologically mediated renal disease by downregulating inflammation during the resolution period.

chemokines; resolution of inflammation; glomerulonephritis