MP29-10 PROTECTIVE EFFECTS OF REGULATORY T CELLS IN RENAL ISCHEMIA/REPERFUSION INJURY IN MICE

Abstract

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I1 Apr 2016MP29-10 PROTECTIVE EFFECTS OF REGULATORY T CELLS IN RENAL ISCHEMIA/REPERFUSION INJURY IN MICE Ryohei Yamamoto, Mitsuru Saito, Hiroshi Tsuruta, Atsushi Maeno, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, Shigeru Satoh, and Tomonori Habuchi Ryohei YamamotoRyohei Yamamoto More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Atsushi MaenoAtsushi Maeno More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1094AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Solid organ transplantation inevitably leads to ischemia/reperfusion injury (IRI). It has recently been reported that IRI may result in not only organ disorders but also secondary disorders by enhanced costimulatory molecules. It is suggested that IRI negatively affects the function and engraftment of a transplanted organ. Regulatory T cells (Tregs) are involved in immunological tolerance at the transplantation site and also have anti-inflammatory effects, including natural immunity. The present study aimed to evaluate whether or not Tregs protect the kidney in IRI and also to investigate the mechanisms involved. METHODS Our IRI model involved 30 min of left renal ischemia in male mice (C57BL/6J, 10-12 weeks); the right kidney was harvested following left renal reperfusion. We administered tricostatin A (TsA) to increase the number of Tregs. Mice were divided into the two groups: The TsA group (N = 11) and the DMSO (vehicle) group (N = 11). TsA (1 mg/kg) and DMSO (1.25 μL/day) were administered intraperitoneally once a day. The drugs were administered to the mice through a period of 7 days before and after IRI. At postoperative day (POD) 7, spleens were harvested, and Treg fractions [CD4(+)Foxp3(+)] were measured by flow cytometry. Serum levels of creatinine and inflammatory cytokines, such as IL-10, IL-6, IL-2, TNF, and IFNγ, were measured by ELISA at PODs 2 and 7. In another group, at 2 days after 30 min of IRI, the left kidney was harvested and stained with PAS to investigate pathological damage as evidenced by the acute tubular necrosis (ATN) score (0-5), and mRNA expressions of Foxp3, IL-10, IL-6, and TGF-B were measured by qRT-PCR. RESULTS Seven days after IRI, the splenic Treg fraction in the TsA group was significantly higher than that in the DMSO group (P < 0.001). The mean level of serum creatinine in the TsA group was significantly lower than that in the DMSO group at POD 2 (P < 0.001) but not at POD7. At POD 2, the mean serum IL-10 level in the TsA group was significantly higher than that in the DMSO group (P < 0.001), whereas the mean serum IL-6 level in the TsA group was significantly lower than that in the DMSO group (P = 0.028). The ATN score in the TsA group was significantly lower than that in the DMSO group (P = 0.017). Foxp3 and IL-10 mRNA expression was significantly higher in the TsA group than that in the DMSO group (P = 0.01 and P = 0.02, respectively). On the other hand, IL-6 mRNA expression was significantly lower in the TsA group than that in the DMSO group (P = 0.01). CONCLUSIONS Increasing the number of Tregs by TsA may reduce early renal dysfunction caused by IRI. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e383 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ryohei Yamamoto More articles by this author Mitsuru Saito More articles by this author Hiroshi Tsuruta More articles by this author Atsushi Maeno More articles by this author Takamitsu Inoue More articles by this author Shintaro Narita More articles by this author Norihiko Tsuchiya More articles by this author Shigeru Satoh More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...