Titre :

MUC1 Mitigates Renal Injury and Inflammation in Endotoxin-Induced Acute Kidney Injury by Inhibiting the TLR4-MD2 Axis and Reducing Pro-inflammatory Macrophages Infiltration

Auteur(s) :

Gibier, Jean-Baptiste [Auteur correspondant]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service de pathologie [CHU Lille]
Swierczewski, Thomas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Csanyi, Marie [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service de pathologie [CHU Lille]
Hemon, Brigitte [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Glowacki, Francois [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service de Néphrologie et Transplantation rénale [CHRU-lille]
Maboudou, Patrice [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Van Seuningen, Isabelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Cauffiez, Christelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Pottier, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Aubert, Sébastien [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service de pathologie [CHU Lille]
Perrais, Michael [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Gnemmi, Viviane [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service de pathologie [CHU Lille]

Titre de la revue :

Shock

Pagination :

629-638

Éditeur :

Lippincott, Williams & Wilkins

Date de publication :

2021-10

ISSN :

1073-2322

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Sepsis is the leading cause of acute kidney injury (AKI) in critical care patients. A cornerstone of sepsis-associated AKI is dysregulated inflammation driven by excessive activation of Toll-like receptor 4 (TLR4) pathway. ...
Lire la suite >Sepsis is the leading cause of acute kidney injury (AKI) in critical care patients. A cornerstone of sepsis-associated AKI is dysregulated inflammation driven by excessive activation of Toll-like receptor 4 (TLR4) pathway. MUC1, a membrane-bound mucin expressed in both epithelial tubular cells and renal macrophages, has been shown to be involved in the regulation of TLRs. Therefore, we hypothesized that MUC1 could mitigate the renal inflammatory response to TLR4 activation. To test this hypothesis, we used a murine model of endotoxin-induced AKI by intraperitoneal injection of LPS. We showed that Muc1−/− mice have a more severe renal dysfunction, an increased activation of the tissular NF-kB pathway and secreted more pro inflammatory cytokines compare to Muc1+/+ mice. By flow cytometry, we observed that the proportion of M1 (pro-inflammatory) macrophages in the kidneys of Muc1−/− mice was significantly increased. In human and murine primary macrophages, we showed that MUC1 is only induced in M1 type macrophages and that macrophages derived from Muc1−/− mice secreted more pro-inflammatory cytokines. Eventually, in HEK293 cells, we showed that MUC1 cytosolic domain (CT) seems necessary for the negative regulation of TLR4 by proximity ligation assay, MUC1-CT is in close relationship with TLR4 and acts as a competitive inhibitor of the recruitment of MYD88. Overall our results support that in the context of endotoxin-induced AKI, MUC1 plays a significant role in controlling disease severity by regulating negatively the TLR4-MD2 axis.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Date de dépôt :

2024-02-17T04:18:22Z