EFFECTS OF GAMMA-INTERFERON ON DR ANTIGEN EXPRESSION, GROWTH, 3,5,3'-TRIIODOTHYRONINE SECRETION, IODIDE UPTAKE, AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE ACCUMULATION IN CULTURED HUMAN THYROID-CELLS

We have examined, using the same system of human thyroid cells in culture, the effects of the cytokine human γ-interferon (γIFN) on the expression of DR antigen, cell proliferation, cAMP accumulation, and the differentiated functions, iodide uptake and T3 secretion. γIFN elicited a dose- and timedependent increase in DR expression, with a maximum effect on day 5 of culture. The cytokine, at the same concentrations and experimental conditions as those found to be effective in inducing DR antigen expression, caused on day 5 of culture a dose-dependent inhibition of [3H]thymidine incorporation, DNA content, cell count, as well as TSH-stimulated (but not basal) iodide uptake and T3 secretion. The γIFN suppressive influence on the differentiated functions was not merely due to a reduction in cell number, but was also apparent when results were expressed per μg DNA. Since the cytokine did not inhibit TSHor forskolin-stimulated cAMP accumulation and showed a suppressive influence toward 8-bromo-cAMP- and forskolin-stimulated T3 secretion, its inhibitory effect seems to be exerted at a site located distal to cAMP formation. Although γIFN alone was devoid of any effect on cAMP accumulation, it enhanced forskolin-stimulated (as well as TSH-activated) cAMP in the presence of 3-isobutyl-l-methylxanthine, an inhibitor of cAMP degradation. Thus, it would seem that γIFN also exerts an influence on cAMP formation (rather than degradation) at a step subsequent to TSH binding to its receptor. The effects we observed seem specific to γIFN, since αIFN, although capable of inhibiting human thyrocyte multiplication, lacked any influence on DR antigen expression, cAMP accumulation, or T3 secretion by human thyroid cells. In what way, if any, is γIFNinduced DR antigen expression on human thyrocytes, an event believed to be critical in the pathophysiology of autoimmune thyroid disease, related to decreased thyroid function and growth is presently unknown. © 1990 by The Endocrine Society.