The human glomerular endothelial cells are potent pro-inflammatory contributors in an <i>in vitro</i> model of lupus nephritis



Dimou, Paraskevi, Wright, Rachael D ORCID: 0000-0002-7606-2297, Budge, Kelly L, Midgley, Angela, Satchell, Simon C, Peak, Matthew ORCID: 0000-0003-1909-3211 and Beresford, Michael W ORCID: 0000-0002-5400-9911
(2019) The human glomerular endothelial cells are potent pro-inflammatory contributors in an <i>in vitro</i> model of lupus nephritis. SCIENTIFIC REPORTS, 9 (1). 8348-.

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Abstract

Juvenile-onset lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients (JSLE). As the exact role of human renal glomerular endothelial cells (GEnCs) in LN has not been fully elucidated, the aim of this study was to investigate their involvement in LN. Conditionally immortalised human GEnCs (ciGEnCs) were treated with pro-inflammatory cytokines known to be involved in LN pathogenesis and also with LPS. Secretion and surface expression of pro-inflammatory proteins was quantified via ELISA and flow cytometry. NF-κΒ and STAT-1 activation was investigated via immunofluorescence. Serum samples from JSLE patients and from healthy controls were used to treat ciGEnCs to determine via qRT-PCR potential changes in the mRNA levels of pro-inflammatory genes. Our results identified TNF-α, IL-1β, IL-13, IFN-γ and LPS as robust in vitro stimuli of ciGEnCs. Each of them led to significantly increased production of different pro-inflammatory proteins, including; IL-6, IL-10, MCP-1, sVCAM-1, MIP-1α, IP-10, GM-CSF, M-CSF, TNF-α, IFN-γ, VCAM-1, ICAM-1, PD-L1 and ICOS-L. TNF-α and IL-1β were shown to activate NF-κB, whilst IFN-γ activated STAT-1. JSLE patient serum promoted IL-6 and IL-1β mRNA expression. In conclusion, our in vitro model provides evidence that human GEnCs play a pivotal role in LN-associated inflammatory process.

Item Type: Article
Uncontrolled Keywords: Adolescent, Autoimmunity, Biomarkers, Cell Adhesion, Cells, Cultured, Chemokines, Child, Endothelial Cells, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Gene Expression Regulation, Humans, Inflammation, Kidney Glomerulus, Lupus Nephritis, Male, NF-kappa B p50 Subunit, STAT1 Transcription Factor
Depositing User: Symplectic Admin
Date Deposited: 11 Jun 2019 13:39
Last Modified: 05 Oct 2023 11:47
DOI: 10.1038/s41598-019-44868-y
Open Access URL: https://doi.org/10.1038/s41598-019-44868-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3045416