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

Research output: Contribution to journalArticle

  • Paraskevi Dimou
  • Rachael D. Wright
  • Kelly L. Budge
  • Angela Midgley
  • Simon C. Satchell
  • Matthew Peak
  • Michael W. Beresford
Original languageEnglish
Article number8348
Number of pages17
JournalScientific Reports
Volume9
Issue number1
Early online date6 Jun 2019
DOIs
DateAccepted/In press - 24 May 2019
DateE-pub ahead of print - 6 Jun 2019
DatePublished (current) - 1 Dec 2019

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.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://doi.org/10.1038/s41598-019-44868-y . Please refer to any applicable terms of use of the publisher.

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