Adenovirus-mediated gene transfer of IL-4 prolongs rat renal allograft survival and inhibits the p21ras-activation pathway

Kato, Hirohisa; Ritter, Thomas; Ke, Bibo; Murakami, Miho; Kusano, Masao; Busuttil, Ronald W.; Kupiec‐Weglinski, Jerzy W.

doi:10.1016/s0041-1345(99)00945-8

Cited by 15 publications

(6 citation statements)

References 4 publications

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“…Overexpression of Th2 cytokines, IL-10 and IL-4 may induce the tolerance. IL-4 gene overexpression prolonged the renal survival (84). In contrast, there is no report to show that IL-10 gene therapy prolongs the survival of the renal allograft, although cardiac and liver allografts are reported to be improved the survival (85,86).…”

Section: Transplantationmentioning

confidence: 95%

Perspectives for Gene Therapy in Renal Diseases

Imai

Isaka

2004

Intern. Med.

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Section: Transplantationmentioning

confidence: 95%

Perspectives for Gene Therapy in Renal Diseases

Imai

Isaka

2004

Intern. Med.

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“…Overexpression of Th2 cytokines, IL-10 and IL-4, may induce the tolerance. IL-4 gene overexpression prolonged the renal survival [32]. In contrast, there is no report to show that IL-10 gene therapy prolongs the survival of the renal allograft, although cardiac and liver allografts were reported to improve the survival [33,34].…”

Section: Transplantationmentioning

confidence: 96%

Gene therapy in renal diseases

Imai¹,

Takabatake

Mizui

et al. 2004

Kidney International

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Kidney-targeted gene therapy could be an ideal treatment for renal diseases since the therapeutic molecule is limited in the kidney and the systemic effect may be minimized. The technical development of the gene delivery to kidney and the identification of the responsive gene for a particular disease encourage the challenge to hereditary diseases. Collagen type IV reassembling was reported to be succeeded in Alport syndrome model by introduction of exogenous COL4A5 gene. Many gene therapies are evaluated in various glomerulonephritis models and unilateral ureteral obstruction (UUO) model, and favorable results are accumulated. Transplant kidney is an ideal target for gene therapy, by which ischemia reperfusion, acute rejection and chronic allograft nephropathy can be treated. The importation of the novel technology, for example hybrid stem cell-gene therapy could promote the gene therapy of renal diseases toward clinical application.

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“…24 Combination of rIL-4 and cyclosporine A extends cardiac allograft survival in rats and syngenic pancreatic islet grafts in non-obese diabetic mice. 26 Moreover, Takeuchi et al 27 demonstrated that murine IL-4 transgenic heart allografts survived longer compared to wild-type hearts with downregulation of intragraft IL-2, whereas Kato et al 28 reported that Ad-IL-4 promoted long-term rat renal allograft survival. On the other hand, there are reports of no difference in heart graft survival in IL-4 knockout mice, 30 that IL-4 treatment fails to affect the survival of syngenic pancreatic islet grafts, 26 and that direct injection of Ad-IL-4 does not prolong rat cardiac allograft survival.…”

Section: Il-4-transduced DC Accelerate Graft Rejectionmentioning

confidence: 99%

“…19,21,22 IL-4 is a Th2 cell-derived cytokine that inhibits IL-2 and IFNg production by Th1 cells, promotes Th2 cell differentiation, and inhibits proinflammatory cytokine (IL-4, IL-6, IL-8 and TNFa) production by monocytes/ macrophages. 23 Several studies that have investigated the role of IL-4 in allograft rejection, either by systemic administration of rIL-4, [24][25][26] use of IL-4 knockout or transgenic mice, 27 or IL-4 gene transfer to the graft, 28 suggest that IL-4 functions to prolong transplant survival. On the other hand, administration of soluble IL-4R delays heart allograft rejection, 29 whereas IL-4-deficient mice can reject allografts with the same vigor as wildtype recipients, and develop the same extent of obliterative vasculopathy as those transplanted to wild-type counterparts.…”

Section: Introductionmentioning

confidence: 99%