Efficacy of interleukin 10 gene hydrofection in pig liver vascular isolated ‘in vivo’ by surgical procedure with interest in liver transplantation
Autoři:
Luis Sendra aff001; María José Herrero aff001; Eva María Montalvá aff003; Inmaculada Noguera aff005; Francisco Orbis aff004; Ana Díaz aff005; Rafael Fernández-Delgado aff006; Rafael López-Andújar aff003; Salvador F. Aliño aff001
Působiště autorů:
Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
aff001; Gene Therapy Unit, Department of Pharmacology, Universitat de Valencia, Valencia, Spain
aff002; Unit of Experimental Hepatology and Liver Transplantation, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
aff003; HPB Surgery and Transplant Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
aff004; SCSIE, Central Services of Experimental Support, Universitat de Valencia, Valencia, Spain
aff005; Pediatrics Unit, Department of Pediatrics, Obstetrics and Gynecology, Universitat de Valencia, Valencia, Spain
aff006; Clinical Pharmacology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
aff007
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224568
Souhrn
Aim
Liver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels.
Methods
hIL10 gene was hydrofected by retrograde hydrodynamic injection in pig liver with complete vascular exclusion mediated by an ‘in vivo’ surgical procedure. Levels of IL10 DNA, RNA and protein were determined within liver tissue 1 and 10 days after the injection and, more frequently, also the interleukin-10 protein in peripheral blood.
Results
The procedure was safe for the animals and neither hemodynamic parameters nor liver function determinations showed relevant alterations. The hIL10 hydrofection in watertight liver mediated efficient gene transfer and this was transcribed and translated to protein, achieving up to 110 pg/ml of IL10 in peripheral blood. This value is close to that considered able to reduce the activity of TNFα by half (IL10 IC50 for TNFα = 124 pg/ml).
Conclusions
Results of this work suggest that IL10 liver hydrofection with vascular exclusion in vivo is a safe and transferable procedure that mediates plasma protein levels with potential clinical interest in immune modulation after transplantation.
Klíčová slova:
Cytokines – Gene delivery – Liver – Liver transplantation – Surgical and invasive medical procedures – Swine – Vascular surgery – Gene transfer
Zdroje
1. Hirschfield G.M., Gibbs P., and Griffiths W.J., Adult liver transplantation: what non-specialists need to know. BMJ, 2009. 338: p. b1670. doi: 10.1136/bmj.b1670 19465469
2. Tedesco D. and Grakoui A., Environmental peer pressure: CD4(+) T cell help in tolerance and transplantation. Liver Transpl, 2018. 24(1): p. 89–97. doi: 10.1002/lt.24873 28926189
3. Ireland S.J., Monson N.L., and Davis L.S., Seeking balance: Potentiation and inhibition of multiple sclerosis autoimmune responses by IL-6 and IL-10. Cytokine, 2015. 73(2): p. 236–44. doi: 10.1016/j.cyto.2015.01.009 25794663
4. Chen W., Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med, 2003. 198(12): p. 1875–86. doi: 10.1084/jem.20030152 14676299
5. Zhang G.Y., Hu M, Wang YM, Alexander SI. Foxp3 as a marker of tolerance induction versus rejection. Curr Opin Organ Transplant, 2009. 14(1): p. 40–5. doi: 10.1097/MOT.0b013e32831da83c 19337145
6. Ziegler S.F., FOXP3: of mice and men. Annu Rev Immunol, 2006. 24: p. 209–26. doi: 10.1146/annurev.immunol.24.021605.090547 16551248
7. Rifle G. and Herve P., Regulatory (suppressor) T cells in peripheral allograft tolerance and graft-versus-host reaction. Transplantation, 2004. 77(1 Suppl): p. S5. doi: 10.1097/01.TP.0000107184.18562.FC 14726759
8. Sendra L., Miguel A, Pérez-Enguix D., Herrero MJ, Montalvá E, García-Gimeno MA, et al., Studying Closed Hydrodynamic Models of "In Vivo" DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans. PLoS One, 2016. 11(10): p. e0163898. doi: 10.1371/journal.pone.0163898 27695064
9. Sendra Gisbert L., Miguel Matas A., Sabater Ortí L., Herrero MJ, Sabater Olivas L, Montalvá Orón EM, et al. Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation. Liver Transpl, 2017. 23(1): p. 50–62. doi: 10.1002/lt.24667 27783460
10. Alberts B, J. A., Lewis J, Raff M, Roberts K, Walter P., From DNA to RNA, in Molecular Biology of the Cell. 2002, Garland Science: New York.
11. Knolle P., Schlaak J, Uhrig A, Kempf P, Meyer zum Büschenfelde KH, Gerken G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J Hepatol, 1995. 22(2): p. 226–9. doi: 10.1016/0168-8278(95)80433-1 7790711
12. Knolle P.A., Uhrig A, Hegenbarth S, Löser E, Schmitt E, Gerken G, et al. IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules. Clin Exp Immunol, 1998. 114(3): p. 427–33. doi: 10.1046/j.1365-2249.1998.00713.x 9844054
13. Breous E., Somanathan S, Vandenberghe LH, Wilson JM. Hepatic regulatory T cells and Kupffer cells are crucial mediators of systemic T cell tolerance to antigens targeting murine liver. Hepatology, 2009. 50(2): p. 612–21. doi: 10.1002/hep.23043 19575456
14. Erhardt A., Biburger M, Papadopoulos T, Tiegs G. IL-10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in mice. Hepatology, 2007. 45(2): p. 475–85. doi: 10.1002/hep.21498 17256743
15. Thomson A.W. and Knolle P.A., Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol, 2010. 10(11): p. 753–66. doi: 10.1038/nri2858 20972472
16. Khanna A., Morelli AE, Zhong C, Takayama T, Lu L, Thomson AW. Effects of liver-derived dendritic cell progenitors on Th1- and Th2-like cytokine responses in vitro and in vivo. J Immunol, 2000. 164(3): p. 1346–54. doi: 10.4049/jimmunol.164.3.1346 10640749
17. Buelens C., Verhasselt V, De Groote D, Thielemans K, Goldman M, Willems F. Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10. Eur J Immunol, 1997. 27(8): p. 1848–52. doi: 10.1002/eji.1830270805 9295017
18. Probst H.C., McCoy K, Okazaki T, Honjo T, van den Broek M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol, 2005. 6(3): p. 280–6. doi: 10.1038/ni1165 15685176
19. Probst H.C., Lagnel J, Kollias G, van den Broek M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity, 2003. 18(5): p. 713–20. doi: 10.1016/s1074-7613(03)00120-1 12753747
20. Matsuno K., Ezaki T, Kudo S, Uehara Y. A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph. J Exp Med, 1996. 183(4): p. 1865–78. doi: 10.1084/jem.183.4.1865 8666943
21. Kudo S., Matsuno K, Ezaki T, Ogawa M. A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation. J Exp Med, 1997. 185(4): p. 777–84. doi: 10.1084/jem.185.4.777 9034155
22. Kamimura K, Suda T, Zhang G, Aoyagi Y, Liu D. Parameters Affecting Image-guided, Hydrodynamic Gene Delivery to Swine Liver. Mol Ther Nucleic Acids. 2013 Oct 15;2:e128 doi: 10.1038/mtna.2013.52 24129227
23. Kamimura K, Suda T, Xu W, Zhang G, Liu D. Image-guided, lobe-specific hydrodynamic gene delivery to swine liver. Mol Ther. 2009 Mar;17(3):491–9 doi: 10.1038/mt.2008.294 19156134
24. Kamimura K, Kanefuji T, Yokoo T, Abe H, Suda T, Kobayashi Y, et al. Safety assessment of liver-targeted hydrodynamic gene delivery in dogs. PLoS One. 2014 Sep 24;9(9):e107203. doi: 10.1371/journal.pone.0107203 25251246
25. Seldon P.M., Barnes P.J., and Giembycz M.A., Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes. Cell Biochem Biophys, 1998. 29(1–2): p. 179–201. doi: 10.1007/BF02737835 9631245
26. Sendra L., Pérez D., Miguel A., Herrero MJ, Noguera I, Díaz A, et al. Human AAT gene transfer to pig liver improved by using a perfusion isolated organ endovascular procedure. Eur Radiol, 2016. 26(1): p. 95–102. doi: 10.1007/s00330-015-3792-2 25911616
27. Tsoulfas G, Takahashi Y, Liu D, Yagnik G, Wu T, Murase N, et al. Hydrodynamic plasmid DNA gene therapy model in liver transplantation. J Surg Res. 2006 Oct;135(2):242–9. doi: 10.1016/j.jss.2006.04.020 16926028
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