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- W2771169999 abstract "Background: Extracellular adenosine triphosphate (ATP) plays a crucial role in promoting inflammatory immune responses. The extracellular ATP can stimulate effector T cells, dendritic cells (DCs) through P2X receptor, and oxidized ATP (oATP), a P2X receptor antagonist, can induce regulatory T cells (Tregs). Here, we investigated whether oATP can attenuate renal ischemia-perfusion injury (IRI). Methods: Bilateral renal IRI was induced in male wild type and RAG-1 knockout (KO) C57BL/6 mice. oATP or PBS was administered intraperitoneally to the mice for 7 consecutive days beginning 6 days before bilateral IRI in a prevention model, or 4 consecutive days beginning 1 day after IRI in a treatment model. Results: In the prevention model, both serum BUN and creatinine on D1 were significantly lower in the oATP than in the PBS. Both tubular injury score and tubular epithelial cell apoptosis were also significantly lower in the oATP. oATP significantly attenuated the infiltration of MHC II+, CD40+, or CD86+ DCs, neutrophils and macrophages into the renal tissue after IRI. It decreased infiltration of activated CD69+CD4+ or CD44+CD4+ T cells, while significantly increased infiltration of Foxp3+CD4+ Tregs in renal tissue. Expression of both IL-6 and CCL2 was reduced in the oATP group. Treg depletion using PC61 abrogated the beneficial effects of oATP. oATP also decreased infiltration of innate immune cells, and attenuated renal functional deterioration after IRI in RAG-1 KO as well as wild type mice. In the treatment model, renal function on D5 was significantly better in the oATP than the PBS. oATP decreased infiltration of innate and adaptive effector cells, and increased inflitration of Foxp3+CD4+ Tregs in renal tissue. In addition, oATP increased renal tubular cell proliferation on D5 and reduced renal fibrosis on D28. Conclusion: oATP can attenuate acute renal damage, and improve renal recovery in IRI by suppressing innate and adaptive immune cells, and inducing Tregs." @default.
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- W2771169999 date "2014-07-01" @default.
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- W2771169999 title "Inhibition of Puringergic Receptors By Oxidized Adenosine Triphosphate Protects the Kidneys Against Ischemia-Reperfusion Injury." @default.
- W2771169999 doi "https://doi.org/10.1097/00007890-201407151-00122" @default.
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