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Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats.
J Heart Lung Transplant. 2006 Dec; 25(12):1474-9.JH

Abstract

BACKGROUND

The prolonged effect of electroporation-mediated human interleukin-10 (hIL-10) overexpression in skeletal muscle under the control of the constitutional polyubiquitin C promoter (pUb hIL-10) on rat lung allograft rejection was evaluated.

METHODS

Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Either 2.5 mug pCIK hIL-10 (hIL-10/cytomegalovirus early promoter enhancer) alone (Group I/sacrifice Day 5 and II/sacrifice Day 10) or in combination with 2.5 mug pUb hIL-10 (hIL-10/UbC promoter; Group III/sacrifice Day 10) were injected into the tibialis anterior muscle of the recipient, followed by electroporation 24 hours before transplantation. Animals in Control Groups IV and V without gene transfer were euthanized on Day 5 and 10, respectively. All animals received a daily non-therapeutic dose of cyclosporine A (2.5 mg/kg).

RESULTS

In Control Group IV, complete rejection (median A3B3) was noted on Day 5 with a Pao(2) of 43 +/- 9 mm Hg. In recipients of Control Group V, measurement of gas exchange on Day 10 and rejection grading was impossible because of complete destruction of the allograft. Group I animals on Day 5 (233 +/- 123 mm Hg; p = 0.02 vs Group IV) and Group II animals on Day 10 (150 +/- 139 mm Hg; p = 0.15 vs Group IV) demonstrated improved graft function. Graft function in Group III was further improved on Day 10 (299 +/- 123 mm Hg; p = 0.002 vs Group IV; p = 0.05 vs Group II; p = 0.36 vs Group I). Rejection was significantly reduced in Group III (median, A2B2) compared with Group II (median, A4B3; p < 0.05).

CONCLUSIONS

Interleukin-10 overexpression under control of the constitutive ubiquitin C promoter ameliorates acute rejection and preserves lung graft function for a prolonged time.

Authors+Show Affiliations

Division of General Thoracic Surgery, University Hospital, Bern, Switzerland. uz.stammberger@insel.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17178344

Citation

Stammberger, Uz, et al. "Prolonged Amelioration of Acute Lung Allograft Rejection By Overexpression of Human Interleukin-10 Under Control of a Long Acting Ubiquitin C Promoter in Rats." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 25, no. 12, 2006, pp. 1474-9.
Stammberger U, Bilici M, Gugger M, et al. Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats. J Heart Lung Transplant. 2006;25(12):1474-9.
Stammberger, U., Bilici, M., Gugger, M., Gazdhar, A., Hamacher, J., Hyde, S. C., & Schmid, R. A. (2006). Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 25(12), 1474-9.
Stammberger U, et al. Prolonged Amelioration of Acute Lung Allograft Rejection By Overexpression of Human Interleukin-10 Under Control of a Long Acting Ubiquitin C Promoter in Rats. J Heart Lung Transplant. 2006;25(12):1474-9. PubMed PMID: 17178344.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats. AU - Stammberger,Uz, AU - Bilici,Murat, AU - Gugger,Mathias, AU - Gazdhar,Amiq, AU - Hamacher,Jürg, AU - Hyde,Stephen C, AU - Schmid,Ralph A, PY - 2006/04/21/received PY - 2006/07/28/revised PY - 2006/09/09/accepted PY - 2006/12/21/pubmed PY - 2007/1/27/medline PY - 2006/12/21/entrez SP - 1474 EP - 9 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J Heart Lung Transplant VL - 25 IS - 12 N2 - BACKGROUND: The prolonged effect of electroporation-mediated human interleukin-10 (hIL-10) overexpression in skeletal muscle under the control of the constitutional polyubiquitin C promoter (pUb hIL-10) on rat lung allograft rejection was evaluated. METHODS: Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Either 2.5 mug pCIK hIL-10 (hIL-10/cytomegalovirus early promoter enhancer) alone (Group I/sacrifice Day 5 and II/sacrifice Day 10) or in combination with 2.5 mug pUb hIL-10 (hIL-10/UbC promoter; Group III/sacrifice Day 10) were injected into the tibialis anterior muscle of the recipient, followed by electroporation 24 hours before transplantation. Animals in Control Groups IV and V without gene transfer were euthanized on Day 5 and 10, respectively. All animals received a daily non-therapeutic dose of cyclosporine A (2.5 mg/kg). RESULTS: In Control Group IV, complete rejection (median A3B3) was noted on Day 5 with a Pao(2) of 43 +/- 9 mm Hg. In recipients of Control Group V, measurement of gas exchange on Day 10 and rejection grading was impossible because of complete destruction of the allograft. Group I animals on Day 5 (233 +/- 123 mm Hg; p = 0.02 vs Group IV) and Group II animals on Day 10 (150 +/- 139 mm Hg; p = 0.15 vs Group IV) demonstrated improved graft function. Graft function in Group III was further improved on Day 10 (299 +/- 123 mm Hg; p = 0.002 vs Group IV; p = 0.05 vs Group II; p = 0.36 vs Group I). Rejection was significantly reduced in Group III (median, A2B2) compared with Group II (median, A4B3; p < 0.05). CONCLUSIONS: Interleukin-10 overexpression under control of the constitutive ubiquitin C promoter ameliorates acute rejection and preserves lung graft function for a prolonged time. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/17178344/Prolonged_amelioration_of_acute_lung_allograft_rejection_by_overexpression_of_human_interleukin_10_under_control_of_a_long_acting_ubiquitin_C_promoter_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(06)00642-5 DB - PRIME DP - Unbound Medicine ER -