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Interleukin‐10 Plasmid Construction and Delivery for the Prevention of Type 1 Diabetes
Author(s) -
LEE MINHYUNG,
PARK HYEWON,
YOUN JEEHEE,
OH EUN TAEX,
KO KYUNGSOO,
KIM SUNGWAN,
PARK YONGSOO
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1375.048
Subject(s) - insulitis , microbiology and biotechnology , transfection , gene delivery , plasmid , enhancer , polyethylenimine , nod mice , interleukin , interleukin 4 , nf κb , genetic enhancement , nod , in vitro , interleukin 10 , in vivo , chemistry , biology , gene expression , diabetes mellitus , immunology , endocrinology , cytokine , gene , inflammation , biochemistry
Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet β cell destruction can be manipulated by the administration of Th 2 cytokines. In this article, the effect of interleukin‐10 (IL‐10) gene delivery was evaluated in vitro and in vivo with a novel IL‐10 plasmid, pSI‐IL‐10‐NFκB. In pSI‐IL‐10‐NFκB, the expression of the IL‐10 gene was driven by the SV40 promotor/enhancer. The nuclear factor κB (NFκB) binding sites were also introduced to facilitate nuclear transport of the plasmid in the cell. In vitro transfection assay with pSI‐IL‐10‐NFκB showed a similar expression level of IL‐10 to the plasmid without NFκB binding sites (pSI‐IL‐10). pSI‐IL‐10‐NFκB and pSI‐IL‐10 were intravenously injected into 5‐week‐old nonobese diabetic (NOD) mice using polyethylenimine (PEI) as a gene carrier. Both groups had persistent gene expression, longer than 5 weeks, and secreted the similarly high IL‐10 serum levels. Interestingly, the degree of insulitis in the pSI‐IL‐10‐NFκB group was improved over the pSI‐IL‐10 group, PEI‐only group, and noninjected controls. The serum glucose levels showed that single injection of pSI‐IL‐10‐NFκB prevented the development of diabetes in 100% of the pSI‐IL‐10‐NFκB–injected animals (5/5), while that of pSI‐IL‐10 prevented diabetes in 40% of the treated animals (2/5). These results suggest that pSI‐IL‐10‐NFκB with PEI can effectively reduce the incidence of insulitis and type 1 diabetes in NOD mice.