Your browser doesn't support javascript.
loading
Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury.
Namwanje, Maria; Bisunke, Bijay; Rousselle, Thomas V; Lamanilao, Gene G; Sunder, Venkatadri S; Patterson, Elizabeth C; Kuscu, Canan; Kuscu, Cem; Maluf, Daniel; Kiran, Manjari; Mas, Valeria; Eason, James D; Bajwa, Amandeep.
Afiliación
  • Namwanje M; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN 38103, USA.
  • Bisunke B; Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Rousselle TV; Department of Genetics, Genomics, and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Lamanilao GG; Department of Surgery, Surgical Sciences Division, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
  • Sunder VS; Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Patterson EC; Department of Systems and Computational Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
  • Kuscu C; Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Kuscu C; Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Maluf D; Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Kiran M; Division of Transplant Surgery, University of Maryland Medical Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
  • Mas V; Department of Systems and Computational Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
  • Eason JD; Department of Surgery, Surgical Sciences Division, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
  • Bajwa A; Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Int J Mol Sci ; 22(10)2021 May 20.
Article en En | MEDLINE | ID: mdl-34065421
Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with rapamycin (10 ng/mL) for 1 h before LPS. In contrast, rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of rapamycin-treated DCs to WT recipients 24 h before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/mL) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Daño por Reperfusión / Sirolimus / Lesión Renal Aguda / Dinámicas Mitocondriales / Isquemia / Mitocondrias Límite: Animals / Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Daño por Reperfusión / Sirolimus / Lesión Renal Aguda / Dinámicas Mitocondriales / Isquemia / Mitocondrias Límite: Animals / Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza