Inhibitory effect of interferon-gamma on the response of human thyrocytes to thyrotropin (TSH) stimulation: relationship between the response to TSH and the expression of DR antigen.
Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.
D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006681:HLA-D Antigens / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D014284:Triiodothyronine / Q000378:metabolism
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D014284:Triiodothyronine; D003994:Bucladesine; D007371:Interferon-gamma; D013972:Thyrotropin; D013954:Thyroglobulin