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The effect of gene therapy using CTLA4Ig/silica‐nanoparticles on canine experimental autoimmune thyroiditis
Author(s) -
Choi Eun Wha,
Shin Il Seob,
Lee Chang Woo,
Youn Hwa Young
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1203
Subject(s) - thyroglobulin , thyroiditis , autoimmune thyroiditis , medicine , peripheral blood mononuclear cell , autoantibody , immunology , cytokine , autoimmune disease , in vitro , endocrinology , antibody , thyroid , chemistry , biochemistry
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‐canine‐thyroglobulin 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. Copyright © 2008 John Wiley & Sons, Ltd.