Coumestrol inhibits autoantibody production through modulating Th1 response in experimental autoimmune thyroiditis

Oncotarget. 2016 Aug 16;7(33):52797-52809. doi: 10.18632/oncotarget.10353.

Abstract

Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 ± 21.74 ng/ml and 135.07 ± 70.40 ng/ml, respectively. In addition, the mice (n = 14-16/group) were immunized twice with thyroglobulin (Tg) and Freund's adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-γ mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity.

Keywords: Immune response; Immunity; Immunology and Microbiology Section; T helper cell; autoimmunity; coumestrol; phytoestrogen; thyroiditis.

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Coumestrol / administration & dosage
  • Coumestrol / pharmacology*
  • Female
  • Freund's Adjuvant / immunology
  • Humans
  • Immunization / methods
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice, Inbred CBA
  • Phytoestrogens / administration & dosage
  • Phytoestrogens / pharmacology
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / metabolism
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Thyroglobulin / immunology*
  • Thyroiditis, Autoimmune / blood
  • Thyroiditis, Autoimmune / immunology*

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Phytoestrogens
  • anti-thyroglobulin
  • Interferon-gamma
  • Freund's Adjuvant
  • Thyroglobulin
  • Coumestrol