Perfluorochemical (PFC) liquid enhances recombinant adenovirus vector-mediated viral interleukin-10 (AdvIL-10) expression in rodent lung
Tóm tắt
Adenovirus and cationic liposome mediated transfer of Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been shown to decrease pro-inflammatory cytokine levels and overall lung inflammation in models of lung transplantation and injury. Limitations to current approaches of IL-10 gene therapy include poor vector delivery methods and pro-inflammatory properties of human IL-10 under certain conditions. We hypothesize that using perfluorochemical (PFC) liquid to deliver the highly homologous viral IL-10 (vIL-10), which is predominantly anti-inflammatory with minimal pro-inflammatory activities, can potentially be a more effective strategy to combat inflammatory lung diseases. In this study, we compare the use of PFC liquid versus aerosolized method to deliver adenovirus encoding the vIL-10 gene (AdvIL-10) in C57Bl6 mice. Detectable vIL-10 levels were measured from bronchoalveolar lavage fluid and lung homogenates at one, four, ten and thirty days after AdvIL-10. Furthermore, we determined if use of PFC liquid could allow for the use of a lower dose of AdvIL-10 by comparing the levels of detectable vIL-10 at different doses of AdvIL-10 delivered +/- PFC liquid. Results showed that PFC liquid enhanced detectable vIL-10 by up to ten fold and that PFC liquid allowed the use of ten-fold less vector. PFC liquid increased detectable vIL-10 in lung homogenates at all time points; however, the increase in detectable vIL-10 in BAL fluid peaked at four days and was no longer evident by thirty days after intratracheal instillation. In summary, this is the first report utilizing PFC liquid to enhance the delivery of a potentially therapeutic molecule, vIL-10. We believe this strategy can be used to perform future studies on the use of the predominantly anti-inflammatory vIL-10 to treat inflammatory lung diseases.
Tài liệu tham khảo
Minter RM, Ferry MA, Murday ME, Tannahill CL, Bahjat FR, Oberholzer C, Oberholzer A, LaFace D, Hutchins B, Wen S: Adenoviral delivery of human and viral IL-10 in murine sepsis. J Immunol. 2001, 167: 1053-1059.
Itano H, Zhang W, Ritter JH, McCarthy TJ, Mohanakumar T, Patterson GA: Adenovirus-mediated gene transfer of human interleukin 10 ameliorates reperfusion injury of rat lung isografts. J Thorac Cardiovasc Surg. 2000, 120: 947-956. 10.1067/mtc.2000.109240.
Qin L, Ding Y, Pahud DR, Robson ND, Shaked A, Bromberg JS: Adenovirus-mediated gene transfer of viral interleukin-10 inhibits the immune response to both alloantigen and adenoviral antigen. Hum Gene Ther. 1997, 8: 1365-1374.
Boehler A, Chamberlain D, Xing Z, Slutsky AS, Jordana M, Gauldie J, Liu M, Keshavjee S: Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous airway obliteration in an animal model of bronchiolitis obliterans. Hum Gene Ther. 1998, 9: 541-551.
Shoji F, Yonemitsu Y, Okano S, Yoshino I, Nakagawa K, Nakashima Y, Hasegawa M, Sugimachi K, Sueishi K: Airway-directed gene transfer of interleukin-10 using recombinant Sendai virus effectively prevents post-transplant fibrous airway obliteration in mice. Gene Ther. 2003, 10: 213-218. 10.1038/sj.gt.3301847.
Hsu DH, Moore KW, Spits H: Differential effects of IL-4 and IL-10 on IL-2-induced IFN-gamma synthesis and lymphokine-activated killer activity. Int Immunol. 1992, 4: 563-569. 10.1093/intimm/4.5.563.
Brain JD, Molina RM, DeCamp MM, Warner AE: Effects of a perfluorochemical emulsion on the fate of circulating Pseudomonas aeruginosa. Am J Physiol. 1999, 276: L1037-1045.
Hsu DH, de Waal Malefyt R, Fiorentino DF, Dang MN, Vieira P, de Vries J, Spits H, Mosmann TR, Moore KW: Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science. 1990, 250: 830-832. 10.1126/science.2173142.
Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR: Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990, 248: 1230-1234. 10.1126/science.2161559.
Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A: IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991, 147: 3815-3822.
Ralph P, Nakoinz I, Sampson-Johannes A, Fong S, Lowe D, Min HY, Lin L: IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol. 1992, 148: 808-814.
de Perrot M, Fischer S, Liu M, Imai Y, Martins S, Sakiyama S, Tabata T, Bai XH, Waddell TK, Davidson BL: Impact of human interleukin-10 on vector-induced inflammation and early graft function in rat lung transplantation. Am J Respir Cell Mol Biol. 2003, 28: 616-625. 10.1165/rcmb.2002-0109OC.
Dokka S, Malanga CJ, Shi X, Chen F, Castranova V, Rojanasakul Y: Inhibition of endotoxin-induced lung inflammation by interleukin-10 gene transfer in mice. Am J Physiol Lung Cell Mol Physiol. 2000, 279: L872-877.
Morrison DF, Foss DL, Murtaugh MP: Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia. Infect Immun. 2000, 68: 4752-4758. 10.1128/IAI.68.8.4752-4758.2000.
Wang P, Wu P, Anthes JC, Siegel MI, Egan RW, Billah MM: Interleukin-10 inhibits interleukin-8 production in human neutrophils. Blood. 1994, 83: 2678-2683.
Riley JK, Takeda K, Akira S, Schreiber RD: Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action. J Biol Chem. 1999, 274: 16513-16521. 10.1074/jbc.274.23.16513.
Itano H, Mora BN, Zhang W, Ritter JH, McCarthy TJ, Yew NS, Mohanakumar T, Patterson GA: Lipid-mediated ex vivo gene transfer of viral interleukin 10 in rat lung allotransplantation. J Thorac Cardiovasc Surg. 2001, 122: 29-38. 10.1067/mtc.2001.114636.
Smith TM, Steinhorn DM, Thusu K, Fuhrman BP, Dandona P: A liquid perfluorochemical decreases the in vitro production of reactive oxygen species by alveolar macrophages. Crit Care Med. 1995, 23: 1533-1539. 10.1097/00003246-199509000-00014.
Steinhorn DM, Rotta AT: Liquid ventilation. Acta Anaesthesiol Scand Suppl. 1997, 111: 140-143.
Steinhorn DM, Papo MC, Rotta AT, Aljada A, Fuhrman BP, Dandona P: Liquid ventilation attenuates pulmonary oxidative damage. J Crit Care. 1999, 14: 20-28. 10.1016/S0883-9441(99)90004-7.
Ruan S, Tate C, Lee JJ, Ritter T, Kolls JK, Shellito JE: Local delivery of the viral interleukin-10 gene suppresses tissue inflammation in murine Pneumocystis carinii infection. Infect Immun. 2002, 70: 6107-6113. 10.1128/IAI.70.11.6107-6113.2002.
Croce MA, Fabian TC, Patton JH, Melton SM, Moore M, Trenthem LL: Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients. J Trauma. 1998, 45: 273-280. discussion 280-272.
Rotta AT, Steinhorn DM: Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury. Crit Care Med. 1998, 26: 1707-1715. 10.1097/00003246-199810000-00026.
Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med. 2003, 348: 138-150. 10.1056/NEJMra021333.
Thomassen MJ, Buhrow LT, Wiedemann HP: Perflubron decreases inflammatory cytokine production by human alveolar macrophages. Crit Care Med. 1997, 25: 2045-2047. 10.1097/00003246-199712000-00023.
Weiss DJ, Bonneau L, Allen JM, Miller AD, Halbert CL: Perfluorochemical liquid enhances adeno-associated virus-mediated transgene expression in lungs. Mol Ther. 2000, 2: 624-630. 10.1006/mthe.2000.0207.
Weiss DJ, Strandjord TP, Jackson JC, Clark JG, Liggitt D: Perfluorochemical liquid-enhanced adenoviral vector distribution and expression in lungs of spontaneously breathing rodents. Exp Lung Res. 1999, 25: 317-333. 10.1080/019021499270222.
Rotta AT, Gunnarsson B, Fuhrman BP, Wiryawan B, Hernan LJ, Steinhorn DM: Perfluorooctyl bromide (perflubron) attenuates oxidative injury to biological and nonbiological systems. Pediatr Crit Care Med. 2003, 4: 233-238. 10.1097/01.PCC.0000059729.21375.D0.
Hotchkiss RS, Tinsley KW, Swanson PE, Chang KC, Cobb JP, Buchman TG, Korsmeyer SJ, Karl IE: Prevention of lymphocyte cell death in sepsis improves survival in mice. Proc Natl Acad Sci USA. 1999, 96: 14541-14546. 10.1073/pnas.96.25.14541.
Naidu B, Krishnadasan B, Whyte RI, Warner RL, Ward PA, Mulligan MS: Regulatory role of IL-10 in experimental obliterative bronchiolitis in rats. Exp Mol Pathol. 2002, 73: 164-170. 10.1006/exmp.2002.2466.
Ding Y, Qin L, Kotenko SV, Pestka S, Bromberg JS: A single amino acid determines the immunostimulatory activity of interleukin 10. J Exp Med. 2000, 191: 213-224. 10.1084/jem.191.2.213.
Oberholzer C, Oberholzer A, Bahjat FR, Minter RM, Tannahill CL, Abouhamze A, LaFace D, Hutchins B, Clare-Salzler MJ, Moldawer LL: Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis. Proc Natl Acad Sci USA. 2001, 98: 11503-11508. 10.1073/pnas.181338198.
Weiss DJ, Beckett T, Bonneau L, Young J, Kolls JK, Wang G: Transient increase in lung epithelial tight junction permeability: an additional mechanism for enhancement of lung transgene expression by perfluorochemical liquids. Mol Ther. 2003, 8: 927-935. 10.1016/j.ymthe.2003.09.003.
Weiss DJ, Baskin GB, Shean MK, Blanchard JL, Kolls JK: Use of perflubron to enhance lung gene expression: safety and initial efficacy studies in non-human primates. Mol Ther. 2002, 5: 8-15. 10.1006/mthe.2001.0507.
Salgar SK, Yang D, Ruiz P, Miller J, Tzakis AG: Viral interleukin-10-engineered autologous hematopoietic stem cell therapy: a novel gene therapy approach to prevent graft rejection. Hum Gene Ther. 2004, 15: 131-144. 10.1089/104303404772679940.