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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/6357046 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832551187445972992 |
|---|---|
| author | Antoine Dewitte Julien Villeneuve Sébastien Lepreux Marion Bouchecareilh Xavier Gauthereau Claire Rigothier Christian Combe Alexandre Ouattara Jean Ripoche |
| author_facet | Antoine Dewitte Julien Villeneuve Sébastien Lepreux Marion Bouchecareilh Xavier Gauthereau Claire Rigothier Christian Combe Alexandre Ouattara Jean Ripoche |
| author_sort | Antoine Dewitte |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5d922b7026b449d293f27cb4e6aa4bbc |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-5d922b7026b449d293f27cb4e6aa4bbc2025-02-03T06:04:38ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/63570466357046CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by ChloroquineAntoine Dewitte0Julien Villeneuve1Sébastien Lepreux2Marion Bouchecareilh3Xavier Gauthereau4Claire Rigothier5Christian Combe6Alexandre Ouattara7Jean Ripoche8Department of Anesthesia and Critical Care, CHU de Bordeaux, F-33600 Pessac, FranceDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, The Keith Peters Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UKINSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, FranceINSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Université de Bordeaux, F-33000 Bordeaux, FranceCNRS, UMR5164, Université de Bordeaux, F-33000 Bordeaux, FranceINSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, FranceINSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, FranceDepartment of Anesthesia and Critical Care, CHU de Bordeaux, F-33600 Pessac, FranceINSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, FranceInflammation 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.http://dx.doi.org/10.1155/2020/6357046 |
| spellingShingle | Antoine Dewitte Julien Villeneuve Sébastien Lepreux Marion Bouchecareilh Xavier Gauthereau Claire Rigothier Christian Combe Alexandre Ouattara Jean Ripoche CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine Mediators of Inflammation |
| title | CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine |
| title_full | CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine |
| title_fullStr | CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine |
| title_full_unstemmed | CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine |
| title_short | CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine |
| title_sort | cd154 induces interleukin 6 secretion by kidney tubular epithelial cells under hypoxic conditions inhibition by chloroquine |
| url | http://dx.doi.org/10.1155/2020/6357046 |
| work_keys_str_mv | AT antoinedewitte cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT julienvilleneuve cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT sebastienlepreux cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT marionbouchecareilh cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT xaviergauthereau cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT clairerigothier cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT christiancombe cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT alexandreouattara cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine AT jeanripoche cd154inducesinterleukin6secretionbykidneytubularepithelialcellsunderhypoxicconditionsinhibitionbychloroquine |