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The effect of gene therapy using CTLA4Ig/silica-nanoparticles on canine experimental autoimmune thyroiditis

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Authors
Choi, Eun Wha; Shin, Il Seob; Lee, Chang Woo; Youn, Hwa Young
Issue Date
2008-05-02
Publisher
Wiley-Blackwell
Citation
J Gene Med 2008; 10: 795-804
Keywords
autoimmune thyroiditisCTLA4Igcytokinedogsemi-quantitativeRT-PCRT cell proliferation
Abstract
Background The present study aimed to determine the effect of canine
CTLA4Ig on canine autoimmune thyroiditis. In a previous study, we
established a canine model of autoimmune thyroiditis by immunizing normal
dogs with bovine thyroglobulin. An in vitro study using recombinant CTLA4Ig
revealed that this protein can inhibit the expression of Th1-type cytokines
and the pro-inflammatory cytokines tested.
Methods As a result of the in vitro study, we constructed therapeutic
CTLA4Ig/silica-nanoparticles and applied them to the treatment of
experimentally induced canine autoimmune thyroiditis.
Results Gene therapy resulted in significant reductions in anti-caninethyroglobulin
autoantibody titer, anti-T4 antibody titer and T-cell proliferation
against thyroglobulin and in the mRNA expressions of interleukin-18
in fresh peripheral blood mononuclear cells (PBMC) from all dogs. There was
also a significant reduction compared to day 0 in tumor necrosis factor-α and
interferon-γ levels in the supernatant from cultured PBMC.
Conclusions The CTLA4Ig-induced suppression of Th1 cytokines is
relatively more significant than it appears because autoimmune thyroiditis is a
Th1-polarized disease. Thus, CTLA4Ig can improve Th1/Th2 cytokine balance
in autoimmune thyroiditis by downregulating Th1 cytokines.
ISSN
1099-498X
Language
English
URI
http://hdl.handle.net/10371/8284
DOI
https://doi.org/10.1002/jgm.1203
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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