Protective Effect of Peptide GV1001 Against Renal Ischemia-Reperfusion Injury in Mice

被引:21
作者
Koo, T. Y. [1 ,2 ]
Yan, J. -J. [1 ]
Yang, J. [1 ,2 ]
机构
[1] Seoul Natl Univ, Coll Med, Transplantat Res Inst, Seoul, South Korea
[2] Seoul Natl Univ Hosp, Transplantat Ctr, Seoul 110744, South Korea
关键词
PHASE-I/II; VACCINATION; CANCER; APOPTOSIS; FAILURE; CELLS; INFLAMMATION; HTERT;
D O I
10.1016/j.transproceed.2013.12.019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Ischemia reperfusion injury (IRI) is a common complication after kidney transplantation. Peptide GV1001 is a peptide vaccine representing a 16 amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity. This study aimed to investigate the potential effects of peptide GV1001 on renal IRI. Methods. Peptide GV1001 was subcutaneously administered to C57BL6/J mice 30 minutes before and 12 hours after bilateral IRI. Sham operation and phosphate-buffered saline (PBS) injection were used as controls. Blood and renal tissues were harvested at 1 day after IRI. Results. Peptide GV1001 treatment significantly attenuated renal functional deterioration after IRI (peptide GV1001 group vs PBS group; blood urea nitrogen, P < .05; creatinine, P < .05). Peptide GV1001 treatment also attenuated renal tissue injury (tubular injury score; the peptide GV1001 group vs PBS group; P < .001). Renal apoptosis was also lower in the peptide GV1001 group. Immunohistochemical studies showed that IRI increased perirenal infiltration of both neutrophils and macrophages, and that peptide GV1001 significantly attenuated this process. Expression of interleukin-6 and monocyte chemotactic protein-1 was significantly reduced by peptide GV1001 treatment. Conclusions. Peptide GV1001 ameliorates acute renal IRI by reducing inflammation and apoptosis; therefore, it is promising as a potential therapeutic agent for renal IRI. The mechanisms of protection should be explored in further studies.
引用
收藏
页码:1117 / 1122
页数:6
相关论文
共 17 条
[1]   Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study [J].
Bernhardt, S. L. ;
Gjertsen, M. K. ;
Trachsel, S. ;
Moller, M. ;
Eriksen, J. A. ;
Meo, M. ;
Buanes, T. ;
Gaudernack, G. .
BRITISH JOURNAL OF CANCER, 2006, 95 (11) :1474-1482
[2]   Role of apoptosis in the pathogenesis of acute renal failure [J].
Bonegio, R ;
Lieberthal, W .
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2002, 11 (03) :301-308
[3]   Ischemic acute renal failure: An inflammatory disease? [J].
Bonventre, JV ;
Zuk, A .
KIDNEY INTERNATIONAL, 2004, 66 (02) :480-485
[4]   Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer [J].
Brunsvig, Paal F. ;
Aamdal, Steinar ;
Gjertsen, Marianne K. ;
Kvalheim, Gunnar ;
Markowski-Grimsrud, Carrie J. ;
Sve, Ingunn ;
Dyrhaug, Marianne ;
Trachsel, Sissel ;
Moller, Mona ;
Eriksen, Jon A. ;
Gaudernack, Gustav .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2006, 55 (12) :1553-1564
[5]  
Daemen MARC, 2002, TRANSPLANTATION, V73, P1693
[6]   Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation [J].
Daemen, MARC ;
van't Veer, C ;
Denecker, G ;
Heemskerk, VH ;
Wolfs, TGAM ;
Clauss, M ;
Vandenabeele, P ;
Buurman, WA .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (05) :541-549
[7]   Update on mechanisms of ischemic acute kidney injury [J].
Devarajan, Prasad .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (06) :1503-1520
[8]   Inflammatory cells in ischemic acute renal failure [J].
Friedewald, JJ ;
Rabb, H .
KIDNEY INTERNATIONAL, 2004, 66 (02) :486-491
[9]   Role of cytokines and chemokines in renal ischemia-reperfusion injury [J].
Furuichi, K ;
Wada, T ;
Yokoyama, H ;
Kobayashi, K .
DRUG NEWS & PERSPECTIVES, 2002, 15 (08) :477-482
[10]   Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001 [J].
Inderberg-Suso, Else-Marit ;
Trachsel, Sissel ;
Lislerud, Kari ;
Rasmussen, Anne-Marie ;
Gaudernack, Gustav .
ONCOIMMUNOLOGY, 2012, 1 (05) :670-686