CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine
Identifieur interne : 000197 ( Main/Exploration ); précédent : 000196; suivant : 000198CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine
Auteurs : Antoine Dewitte [France] ; Julien Villeneuve [Royaume-Uni] ; Sébastien Lepreux [France] ; Marion Bouchecareilh [France] ; Xavier Gauthereau [France] ; Claire Rigothier [France] ; Christian Combe [France] ; Alexandre Ouattara [France] ; Jean Ripoche [France]Source :
- Mediators of Inflammation [ 0962-9351 ] ; 2020.
Abstract
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.
Url:
DOI: 10.1155/2020/6357046
PubMed: 32089648
PubMed Central: 7013356
Affiliations:
- France, Royaume-Uni
- Angleterre, Angleterre de l'Est, Aquitaine, Nouvelle-Aquitaine
- Bordeaux, Cambridge, Libourne, Pessac
- Université de Bordeaux, Université de Cambridge
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Le document en format XML
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Critical Care, CHU de Bordeaux, F-33600 Pessac, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Anesthesia and Critical Care, CHU de Bordeaux, F-33600 Pessac</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Pessac</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="I2">INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Villeneuve, Julien" sort="Villeneuve, Julien" uniqKey="Villeneuve J" first="Julien" last="Villeneuve">Julien Villeneuve</name><affiliation wicri:level="4"><nlm:aff id="I3">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, The Keith Peters Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, The Keith Peters Building, Cambridge Biomedical Campus, Cambridge CB2 0XY</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Lepreux, Sebastien" sort="Lepreux, Sebastien" uniqKey="Lepreux S" first="Sébastien" last="Lepreux">Sébastien Lepreux</name><affiliation wicri:level="4"><nlm:aff id="I2">INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="I4">Pathology Unit, CH de Libourne, F-33505 Libourne, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pathology Unit, CH de Libourne, F-33505 Libourne</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Libourne</settlement></placeName></affiliation></author><author><name sortKey="Bouchecareilh, Marion" sort="Bouchecareilh, Marion" uniqKey="Bouchecareilh M" first="Marion" last="Bouchecareilh">Marion Bouchecareilh</name><affiliation wicri:level="4"><nlm:aff id="I5">INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Gauthereau, Xavier" sort="Gauthereau, Xavier" uniqKey="Gauthereau X" first="Xavier" last="Gauthereau">Xavier Gauthereau</name><affiliation wicri:level="4"><nlm:aff id="I6">CNRS, UMR5164, Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS, UMR5164, Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Rigothier, Claire" sort="Rigothier, Claire" uniqKey="Rigothier C" first="Claire" last="Rigothier">Claire Rigothier</name><affiliation wicri:level="4"><nlm:aff id="I2">INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="I7">Department of Nephrology-Transplantation-Dialysis, CHU de Bordeaux, F-33076 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Nephrology-Transplantation-Dialysis, CHU de Bordeaux, F-33076 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Combe, Christian" sort="Combe, Christian" uniqKey="Combe C" first="Christian" last="Combe">Christian Combe</name><affiliation wicri:level="4"><nlm:aff id="I2">INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="I7">Department of Nephrology-Transplantation-Dialysis, CHU de Bordeaux, F-33076 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Nephrology-Transplantation-Dialysis, CHU de Bordeaux, F-33076 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Ouattara, Alexandre" sort="Ouattara, Alexandre" uniqKey="Ouattara A" first="Alexandre" last="Ouattara">Alexandre Ouattara</name><affiliation wicri:level="3"><nlm:aff id="I1">Department of Anesthesia and Critical Care, CHU de Bordeaux, F-33600 Pessac, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Anesthesia and Critical Care, CHU de Bordeaux, F-33600 Pessac</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Pessac</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="I8">INSERM, UMR1034 Biology of Cardiovascular Diseases, Université de Bordeaux, F-33600 Pessac, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1034 Biology of Cardiovascular Diseases, Université de Bordeaux, F-33600 Pessac</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Pessac</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Ripoche, Jean" sort="Ripoche, Jean" uniqKey="Ripoche J" first="Jean" last="Ripoche">Jean Ripoche</name><affiliation wicri:level="4"><nlm:aff id="I2">INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR1026 Bioingénierie Tissulaire (Biotis), Université de Bordeaux, F-33000 Bordeaux</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author></analytic><series><title level="j">Mediators of Inflammation</title><idno type="ISSN">0962-9351</idno><idno type="eISSN">1466-1861</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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 (O<sub>2</sub>) 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 O<sub>2</sub> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Taylor, C T" uniqKey="Taylor C">C. T. Taylor</name></author><author><name sortKey="Doherty, G" uniqKey="Doherty G">G. Doherty</name></author><author><name sortKey="Fallon, P G" uniqKey="Fallon P">P. G. Fallon</name></author><author><name sortKey="Cummins, E P" uniqKey="Cummins E">E. P. Cummins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eltzschig, H K" uniqKey="Eltzschig H">H. K. 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Byun</name></author><author><name sortKey="Jue, D M" uniqKey="Jue D">D. M. Jue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weber, S M" uniqKey="Weber S">S. M. Weber</name></author><author><name sortKey="Levitz, S M" uniqKey="Levitz S">S. M. Levitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jeong, J Y" uniqKey="Jeong J">J. Y. Jeong</name></author><author><name sortKey="Jue, D M" uniqKey="Jue D">D. M. Jue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, S F" uniqKey="Wu S">S. F. Wu</name></author><author><name sortKey="Chang, C B" uniqKey="Chang C">C. B. Chang</name></author><author><name sortKey="Hsu, J M" uniqKey="Hsu J">J. M. Hsu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Aquitaine</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Bordeaux</li><li>Cambridge</li><li>Libourne</li><li>Pessac</li></settlement><orgName><li>Université de Bordeaux</li><li>Université de Cambridge</li></orgName></list><tree><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Dewitte, Antoine" sort="Dewitte, Antoine" uniqKey="Dewitte A" first="Antoine" last="Dewitte">Antoine Dewitte</name></region><name sortKey="Bouchecareilh, Marion" sort="Bouchecareilh, Marion" uniqKey="Bouchecareilh M" first="Marion" last="Bouchecareilh">Marion Bouchecareilh</name><name sortKey="Combe, Christian" sort="Combe, Christian" uniqKey="Combe C" first="Christian" last="Combe">Christian Combe</name><name sortKey="Combe, Christian" sort="Combe, Christian" uniqKey="Combe C" first="Christian" last="Combe">Christian Combe</name><name sortKey="Dewitte, Antoine" sort="Dewitte, Antoine" uniqKey="Dewitte A" first="Antoine" last="Dewitte">Antoine Dewitte</name><name sortKey="Gauthereau, Xavier" sort="Gauthereau, Xavier" uniqKey="Gauthereau X" first="Xavier" last="Gauthereau">Xavier Gauthereau</name><name sortKey="Lepreux, Sebastien" sort="Lepreux, Sebastien" uniqKey="Lepreux S" first="Sébastien" last="Lepreux">Sébastien Lepreux</name><name sortKey="Lepreux, Sebastien" sort="Lepreux, Sebastien" uniqKey="Lepreux S" first="Sébastien" last="Lepreux">Sébastien Lepreux</name><name sortKey="Ouattara, Alexandre" sort="Ouattara, Alexandre" uniqKey="Ouattara A" first="Alexandre" last="Ouattara">Alexandre Ouattara</name><name sortKey="Ouattara, Alexandre" sort="Ouattara, Alexandre" uniqKey="Ouattara A" first="Alexandre" last="Ouattara">Alexandre Ouattara</name><name sortKey="Rigothier, Claire" sort="Rigothier, Claire" uniqKey="Rigothier C" first="Claire" last="Rigothier">Claire Rigothier</name><name sortKey="Rigothier, Claire" sort="Rigothier, Claire" uniqKey="Rigothier C" first="Claire" last="Rigothier">Claire Rigothier</name><name sortKey="Ripoche, Jean" sort="Ripoche, Jean" uniqKey="Ripoche J" first="Jean" last="Ripoche">Jean Ripoche</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Villeneuve, Julien" sort="Villeneuve, Julien" uniqKey="Villeneuve J" first="Julien" last="Villeneuve">Julien Villeneuve</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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