Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines

Granger, Rachel L, Hughes, Timothy Richard ORCID: https://orcid.org/0000-0003-2348-3490 and Ramji, Dipak Purshottam ORCID: https://orcid.org/0000-0002-6419-5578 2000. Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines. Biochimica et Biophysica Acta - Molecular Basis of Disease 1501 (2-3) , pp. 171-179. 10.1016/S0925-4439(00)00016-8

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Abstract

Binding sites for the CCAAT-enhancer binding protein (C/EBP) family are present in the promoter regions of several genes that are known to be expressed by mesangial cells (MC) during the pathogenesis of glomerular inflammatory diseases. The precise regulation of the C/EBP family by agents that are known to activate MC is, however, poorly understood. We report here the action of interleukin-1 (IL)-1 and, for the first time, lipopolysaccharide (LPS), platelet-derived growth factor (PDGF), IL-6, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) on the C/EBP expression profile and functional DNA binding activity in primary rat MC. Both cell-type- and stimulus-specific regulation of C/EBP mRNA expression and DNA binding activity were identified, with C/EBPα being induced by LPS, C/EBPβ by LPS, IL-1, TNF-α and C/EBPδ by LPS, IL-1, IFN-γ, TNF-α and PDGF. Such differential regulation, particularly that of C/EBPβ, may be responsible for the mediator-specific differences in the expression of C/EBP-regulated genes in MC. Additionally, the involvement of potential post-transcriptional mechanisms in the regulation of C/EBPδ were identified. These studies provide novel insights into the stimulus-specific regulation of gene expression during renal diseases.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0925-4439
Last Modified:	27 Oct 2022 08:48
URI:	https://orca.cardiff.ac.uk/id/eprint/63452

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