Reduction in Renal Ischemia-Reperfusion Injury in Mice by a Phosphoinositide 3-Kinase p110gamma-Specific Inhibitor.

Autor:	Kim N; 1 Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 2 Department of Medicine Graduate School, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 3 Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, South Korea. 4 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 5 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Woo DC, Joo SJ, Song Y, Lee JJ, Woo CW, Kim ST, Hong S, Cho YM, Han DJ
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2015 Oct; Vol. 99 (10), pp. 2070-6.
DOI:	10.1097/TP.0000000000000742
Abstrakt:	Background: Although renal ischemia-reperfusion injury (IRI) can cause delayed graft function, a targeted therapy is not yet available. Because phosphoinositide 3-kinases (PI3K) p110γ and p110δ play important roles in immune cell migration and function, we investigated the effects of PI3K p110γ- and p110δ-specific inhibitors in a murine renal IRI model. Methods: Renal function was assessed by serum creatine and hematoxylin-eosin staining. Immune cell migration was assessed by flow cytometry and an in vitro cell migration assay using Transwell plates. Gene expression analysis and a multiplex cytokine/chemokine assay were performed to find cytokines/chemokines whose expression was upregulated in renal IRI and affected by p110γ-specific inhibitor. Results: The PI3K p110γ-specific inhibitor, but not p110δ-specific inhibitor, significantly reduced serum creatine levels and acute tubular necrosis. These were accompanied by reduced infiltration of B cells and reduced expression of CXCL9, a CXCR3 ligand, suggesting that p110γ plays an important role in B-cell migration toward injured kidneys. An in vitro cell migration assay revealed for the first time that B-cell migration to injured kidney cells and to CXCL9 requires p110γ. Conclusions: p110γ-specific inhibitor ameliorates renal IRI by reducing necrosis and immune cell migration. This inhibitor may have the potential to reduce renal graft failure caused by renal IRI.
Databáze:	MEDLINE
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