The mechanism of action of tumour necrosis factor-α and interleukin 1 on FRTL-5 rat thyroid cells

Abstract

Previous work showed that treatment of rats with tumour necrosis factor-alpha produced a model of nonthyroid illness in which there was reduction of circulating thyroid hormones and TSH, reduced thyroid response to TSH, and reduced thyroid iodide uptake. In vitro studies showed that tumour necrosis factor-alpha binds to a specific receptor on FRTL-5 rat thyroid cells, that TSH increases the number of tumour necrosis factor-alpha receptors, and that tumour necrosis factor-alpha inhibits iodide uptake by these cells. In the present study, we obtained additional data on the effects of tumour necrosis factor-alpha on FRTL-5 cells and studied the mechanism of action of tumour necrosis factor-alpha in these cells. Tumour necrosis factor-alpha inhibited both basal and TSH-stimulated [125I]iodide uptake: tumour necrosis factor-alpha slowed the recovery of [125I]iodide trapping after the cells were exposed to TSH and augmented the loss of the [125I]iodide trapping function after the cells were deprived of TSH: tumour necrosis factor-alpha inhibited [125I]iodide trapping in a noncompetitive manner; tumour necrosis factor-alpha did not affect cell growth of FRTL-5 cells. Interleukin-1 (IL-1) also inhibited basal and TSH-stimulated [125I]iodide uptake, but it stimulated cell growth. Tumour necrosis factor-alpha and IL-1 did not affect the generation of cAMP in the presence or absence of TSH; these cytokines blocked the cAMP-induced stimulation of [125I]iodide uptake. Tumour necrosis factor-alpha did not affect [3H]arachidonic acid uptake or release by FRTL-5 cells. The inhibitors of the phospholipase A2-arachidonic acid pathway did not affect the action of tumour necrosis factor-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)