Liposome-mediated transfer of IL-1 receptor antagonist gene to dispersed islet cells does not prevent recurrence of disease in syngeneically transplanted NOD mice.
IL-1beta is cytotoxic to pancreatic beta-cells in vitro but its role in the vicinity of beta-cells in vivo is unknown. We explored whether liposome-mediated transfer of the interleukin 1 receptor antagonist (IL-1ra) gene to islet cells might prevent recurrence of disease in syngeneically transplanted non-obese diabetic (NOD) mice. NOD mouse islet cells were transfected using liposome-mediated gene transfer with a human IL-1ra cDNA construct and transplanted two days later to prediabetic NOD mice. Graft infiltration and destruction were monitored three, five and eight days posttransplantation by histology and determination of insulin and cytokine content. IL-1ra gene transfer resulted in transient expression of IL-1ra protein in islet cells in vitro as assessed by ELISA and of IL-1ra mRNA in transplanted islets as revealed by RT-PCR. However, both control and IL-1ra transfected NOD grafts exhibited massive infiltration and loss of insulin-positive cells, paralleled by a decreased insulin content. Increased IL-1ra expression did not clearly affect other cytokine profiles (IL-1beta, IFN-gamma, IL-2), except for an increase of IL-10 on day eight. In conclusion, liposome-mediated IL-1ra gene transfer to mouse islet cells results in transient expression of IL-1ra which is, however, insufficient to confer resistance to destruction of grafted insulin-producing cells in the NOD mouse.
Saldeen
J
J
Department of Medical Cell Biology, Uppsala University, Sweden. Johan.Saldeen@medcellbiol.uu.se
Sandler
S
S
Bendtzen
K
K
Welsh
N
N
D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008081:Liposomes; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D012008:Recurrence; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D008081:Liposomes; D012795:Sialoglycoproteins