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

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-alpha and interferon-gamma 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.

• Authors: Eun Wha Choi, Il Seob Shin, Chang Woo Lee, Hwa Young Youn
• Journal: The journal of gene medicine (J Gene Med) Vol. 10 Issue 7 Pg. 795-804 (Jul 2008) ISSN: 1521-2254 [Electronic] England
• PMID: 18452240 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• DNA Primers
• Immunoconjugates
• Interleukin-18
• Tumor Necrosis Factor-alpha
• Silicon Dioxide
• Abatacept
• Interferon-gamma

Topics

• Abatacept
• Animals
• Cell Proliferation
• Cytokines (antagonists & inhibitors)
• DNA Primers (genetics)
• Dogs
• Enzyme-Linked Immunosorbent Assay
• Genetic Therapy (methods)
• Immunoconjugates (immunology, therapeutic use)
• Interferon-gamma (metabolism)
• Interleukin-18 (blood)
• Leukocytes, Mononuclear (metabolism)
• Nanoparticles (therapeutic use)
• Reverse Transcriptase Polymerase Chain Reaction
• Silicon Dioxide
• T-Lymphocytes (cytology)
• Thyroiditis, Autoimmune (therapy)
• Tumor Necrosis Factor-alpha (metabolism)