Interferon interactions with thyroid cells

Iodide uptake by functioning rat thyroid (FRTL) cells is increased by mouse interferon. The effect is detectable using purified interferon; it is not accompanied by an increase in intracellular cyclic AMP levels, is measurable within 20 min, and is prevented by cholera toxin, an agent which inhibits interferon's antiviral activity. The effect of interferon is biphasic with maximally increased iodide uptake (approximately 2-fold) evident at about 300 international mouse units per ml (U/ml) and lesser effects evident at higher concentrations (greater than 1000 U/ml). The effect of mouse interferon on iodide uptake is accompanied by an extremely sensitive antiviral response. Thus, significant antiviral protection is evident at 1 U/ml with FRTL cells, as opposed to 1000 U/ml for nonfunctioning rat thyroid (FRT) cells. Functioning FRTL thyroid cells are also more sensitive to mouse interferon (10-fold) with respect to 2',5'-polyadenylate (An) synthetase activity or to 125I-thyrotropin binding to membrane preparations than are nonfunctioning FRT cells. Antiviral protection in FRTL cells is evident as early as 1 h after exposure to mouse interferon, and is accompanied by a nearly 100-fold increase in the measurable titer of 2'5'-An synthetase activity. Actinomycin D blocks the antiviral effect of interferon, but not its effect on iodide uptake. The results are discussed with respect to the unusually sensitive response of heterologous (rat) cells to mouse interferon: a possible relationship between thyrotropin and interferon receptors; and, the difference in interferon sensitivity exhibited by differentiated (functioning) as opposed to undifferentiated (nonfunctioning) thyroid cells.