Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases.

TY - JOUR

T1 - Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases.

AU - Panzer, Ulf

AU - Steinmetz, Oliver

AU - Turner, Jan Eric

AU - Meyer-Schwesinger, Catherine

AU - von Ruffer, Claudia

AU - Meyer, Tobias N

AU - Zahner, Gunther

AU - Gómez-Guerrero, Carmen

AU - Schmid, Roland M

AU - Helmchen, Udo

AU - Moeckel, Gilbert W

AU - Wolf, Gunter

AU - Stahl, Rolf A.K.

AU - Thaiss, Friedrich

PY - 2009

Y1 - 2009

N2 - In renal tissue injury, activation of the transcription factor NF-kappa B has a central role in the induction of pro-inflammatory gene expression, which are involved in the development of progressive renal inflammatory disease. The function of NF-kappa 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-kappa B in two different models of acute nephritis. Our experiments demonstrate a biphasic activation of NF-kappa 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-kappa 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 as NF-kappa 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-kappa B subunit p50 proteins have critical in vivo functions in immunologically mediated renal disease by downregulating inflammation during the resolution period. Key words: renal inflammation, chemokines, resolution of inflammation, NF-kappa B.

AB - In renal tissue injury, activation of the transcription factor NF-kappa B has a central role in the induction of pro-inflammatory gene expression, which are involved in the development of progressive renal inflammatory disease. The function of NF-kappa 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-kappa B in two different models of acute nephritis. Our experiments demonstrate a biphasic activation of NF-kappa 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-kappa 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 as NF-kappa 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-kappa B subunit p50 proteins have critical in vivo functions in immunologically mediated renal disease by downregulating inflammation during the resolution period. Key words: renal inflammation, chemokines, resolution of inflammation, NF-kappa B.

M3 - SCORING: Zeitschriftenaufsatz

JO - AM J PHYSIOL-RENAL

JF - AM J PHYSIOL-RENAL

SN - 1931-857X

ER -