CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine

Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an ess...

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Veröffentlicht in:Mediators of inflammation Jg. 2020; H. 2020; S. 1 - 14
Hauptverfasser: Ripoche, Jean, Ouattara, Alexandre, Rigothier, Claire, Gauthereau, Xavier, Bouchecareilh, Marion, Lepreux, Sébastien, Villeneuve, Julien, Dewitte, Antoine, Combe, Christian
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Cairo, Egypt Hindawi Publishing Corporation 2020
Hindawi
John Wiley & Sons, Inc
Wiley
Schlagworte:
Analysis
Anti-inflammatory agents
Biotechnology industry
CD40 antigen
CD40L protein
Cell culture
Chloroquine
Cytokines
Epithelial cells
Epithelium
Experiments
Gene expression
Hypoxia
Inflammation
Interleukin 6
Interleukins
Ischemia
Kidneys
Life Sciences
Platelets
RNA
Transcription
Tumor necrosis factor-TNF
France
United States
United States > US
ISSN:0962-9351, 1466-1861, 1466-1861
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Zusammenfassung:Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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PMCID: PMC7013356
Academic Editor: Michele T. Pritchard
ISSN:0962-9351
1466-1861
1466-1861
DOI:10.1155/2020/6357046