Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.

The neutrophil gelatinase-associated lipocalin 2 (LCN2) is a critical inflammatory mediator persistently induced during endotoxemia, contributing to tubular damage and kidney failure. The intracellular process responsible for persistent induction of LCN2 by bacterial endotoxin Lipopolysaccharide (LP...

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Autores principales:	Trevor Glaros, Yan Fu, Jianhua Xing, Liwu Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fcc0969b528841bea4b0985db5f34a61
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spelling	oai:doaj.org-article:fcc0969b528841bea4b0985db5f34a612021-11-18T07:22:17ZMolecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.1932-620310.1371/journal.pone.0034633https://doaj.org/article/fcc0969b528841bea4b0985db5f34a612012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514649/?tool=EBIhttps://doaj.org/toc/1932-6203The neutrophil gelatinase-associated lipocalin 2 (LCN2) is a critical inflammatory mediator persistently induced during endotoxemia, contributing to tubular damage and kidney failure. The intracellular process responsible for persistent induction of LCN2 by bacterial endotoxin Lipopolysaccharide (LPS) is not well understood. Using primary kidney fibroblasts, we observed that LPS-induced LCN2 expression requires a coupled circuit involving an early transient phase of AP-1 path and a late persistent phase of C/EBPδ path, both of which are dependent upon the interleukin 1 receptor associated kinase 1 (IRAK-1). Using immunoprecipitation analysis we observed transient binding of AP-1 to the promoters of both TNFα and C/ebpδ. On the other hand, we only observed persistent binding of C/EBPδ to its own promoter but not on TNFα. Blockage of new protein synthesis using cyclohexamide significantly reduced the expression of C/EBPδ as well as LCN2. By chromatin immunoprecipitation analyses, we demonstrated that LPS recruited C/EBPδ to the Lcn2 promoter in WT, but not IRAK-1 deficient fibroblasts. A differential equation-based computational model captured the dynamic circuit leading to the persistent induction of LCN2. In vivo, we observed elevated levels of LCN2 in kidneys harvested from LPS-injected WT mice as compared to IRAK-1 deficient mice. Taken together, this study has identified an integrated intracellular network involved in the persistent induction of LCN2 by LPS.Trevor GlarosYan FuJianhua XingLiwu LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34633 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Trevor Glaros Yan Fu Jianhua Xing Liwu Li Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.
description	The neutrophil gelatinase-associated lipocalin 2 (LCN2) is a critical inflammatory mediator persistently induced during endotoxemia, contributing to tubular damage and kidney failure. The intracellular process responsible for persistent induction of LCN2 by bacterial endotoxin Lipopolysaccharide (LPS) is not well understood. Using primary kidney fibroblasts, we observed that LPS-induced LCN2 expression requires a coupled circuit involving an early transient phase of AP-1 path and a late persistent phase of C/EBPδ path, both of which are dependent upon the interleukin 1 receptor associated kinase 1 (IRAK-1). Using immunoprecipitation analysis we observed transient binding of AP-1 to the promoters of both TNFα and C/ebpδ. On the other hand, we only observed persistent binding of C/EBPδ to its own promoter but not on TNFα. Blockage of new protein synthesis using cyclohexamide significantly reduced the expression of C/EBPδ as well as LCN2. By chromatin immunoprecipitation analyses, we demonstrated that LPS recruited C/EBPδ to the Lcn2 promoter in WT, but not IRAK-1 deficient fibroblasts. A differential equation-based computational model captured the dynamic circuit leading to the persistent induction of LCN2. In vivo, we observed elevated levels of LCN2 in kidneys harvested from LPS-injected WT mice as compared to IRAK-1 deficient mice. Taken together, this study has identified an integrated intracellular network involved in the persistent induction of LCN2 by LPS.
format	article
author	Trevor Glaros Yan Fu Jianhua Xing Liwu Li
author_facet	Trevor Glaros Yan Fu Jianhua Xing Liwu Li
author_sort	Trevor Glaros
title	Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.
title_short	Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.
title_full	Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.
title_fullStr	Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.
title_full_unstemmed	Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.
title_sort	molecular mechanism underlying persistent induction of lcn2 by lipopolysaccharide in kidney fibroblasts.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/fcc0969b528841bea4b0985db5f34a61
work_keys_str_mv	AT trevorglaros molecularmechanismunderlyingpersistentinductionoflcn2bylipopolysaccharideinkidneyfibroblasts AT yanfu molecularmechanismunderlyingpersistentinductionoflcn2bylipopolysaccharideinkidneyfibroblasts AT jianhuaxing molecularmechanismunderlyingpersistentinductionoflcn2bylipopolysaccharideinkidneyfibroblasts AT liwuli molecularmechanismunderlyingpersistentinductionoflcn2bylipopolysaccharideinkidneyfibroblasts
_version_	1718423574814916608

Molecular mechanism underlying persistent induction of LCN2 by lipopolysaccharide in kidney fibroblasts.

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