RRC ID 1604
Author Saitoh O, Mizutori Y, Takamura N, Yamasaki H, Kita A, Kuwahara H, Nagayama Y.
Title Adenovirus-mediated gene delivery of interleukin-10, but not transforming growth factor beta, ameliorates the induction of Graves' hyperthyroidism in BALB/c mice.
Journal Clin Exp Immunol
Abstract Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are well known anti-inflammatory cytokines. We have studied the effect of adenovirus-mediated IL-10 and TGF-beta gene delivery on the induction of Graves' hyperthyroidism in our mouse model that involves repeated injections of adenovirus expressing the thyrotropin receptor A subunit (AdTSHR). We first constructed adenoviruses encoding the two cytokines (AdIL10 and AdTGF(beta)) and confirmed expression by in vitro infection of COS cells. Susceptible BALB/c mice were injected twice with AdTSHR alone or together with AdIL10 or AdTGF(beta), and bled two weeks after the second immunization. Significantly elevated serum thyroxine levels were seen in 26% of mice immunized with AdTSHR and AdIL10 versus 61% with AdTSHR alone. Levels of thyroid stimulating antibody, but not nonstimulating antibody, were also decreased, and TSHR-specific splenocyte secretion of interferon-gamma in recall assays was impaired in mice treated with AdIL10. In contrast, AdTGF(beta) had little effect on hyperthyroidism. Overall, our findings demonstrate that gene delivery of IL-10, but not TGF-beta, suppresses the induction of Graves' hyperthyroidism in a mouse model. However, the effect of IL-10 is less powerful than we observed previously with T helper type 2-inducers including adenovirus expressing IL-4, Shistosoma mansoni infection or alpha-galactosylceramide.
Volume 141(3)
Pages 405-11
Published 2005-9-1
DOI 10.1111/j.1365-2249.2005.02874.x
PMID 16045729
PMC PMC1809459
MeSH Adenoviridae / genetics Animals Antibodies / immunology Autoantibodies / immunology* Female Genetic Vectors / administration & dosage Graves Disease / immunology* Immunoglobulins, Thyroid-Stimulating / immunology Interleukin-10 / genetics Interleukin-10 / immunology* Mice Mice, Inbred BALB C Models, Animal Protein Binding Receptors, Thyrotropin / immunology Thyroid Gland / immunology Transduction, Genetic / methods Transforming Growth Factor beta / genetics Transforming Growth Factor beta / immunology*
IF 3.532
Times Cited 10
DNA material pBluescript SKII+mIL10 (RDB01476)