IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jack B CowlandNiels Borregaard

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding protein that exerts a bacteriostatic effect by sequestering iron. Strong induction of NGAL synthesis has been observed in inflamed epithelium of the lungs and colon. Expression of NGAL is up-regulated in the lung epithelial cell line A549 by IL-1beta, but not by TNF-alpha, despite an induction of NF-kappaB binding to the NGAL promoter by both cytokines. In this study, we present evidence that the IL-1beta specificity is caused by a requirement of the NGAL promoter for the NF-kappaB-binding cofactor IkappaB-zeta for transcriptional activation. Up-regulation of NGAL expression in A549 cells following IL-1beta stimulation was dependent on de novo protein synthesis and was greatly diminished by a small interfering against IkappaB-zeta mRNA. Cotransfection of A549 cells with a plasmid expressing IkappaB-zeta made TNF-alpha capable of inducing NGAL transcription, indicating that IkappaB-zeta induction is the only factor discriminating between IL-1beta and TNF-alpha in their ability to induce NGAL expression. Coexpression of the cofactor Bcl-3, which is closely related to IkappaB-zeta, did not enable TNF-alpha to induce NGAL transcription. A functional NF-kappa...Continue Reading

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Citations

Sep 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alessio IannettiAntonio Leonardi
Nov 15, 2008·Journal of Cellular Biochemistry·Grit SommerMathias Fasshauer
Apr 8, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Max SieberAngela Mally
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yvonne R ChanJay K Kolls
Aug 27, 2009·PloS One·Raquel M RaicesMark D Wewers
Sep 11, 2010·Clinical Journal of the American Society of Nephrology : CJASN·Linjun CaiShengyuan Xu
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May 22, 2013·International Journal of Endocrinology·Kunihiro Sakuma, Akihiko Yamaguchi
Jul 22, 2014·Liver International : Official Journal of the International Association for the Study of the Liver·Katrin Kienzl-WagnerHerbert Tilg
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