THE SODIUM-IODIDE SYMPORTER GENE AND ITS REGULATION BY CYTOKINES FOUND IN AUTOIMMMUNITY

Iodide concentration by the thyroid gland, an essential step for thyro id hormone synthesis, is mediated by the Na+/I- symporter (NIS). To id entify factors that may regulate this process, we have studied NIS gen e expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-qu antitative reverse transcription-polymerase chain reaction (RT-PCR) te chnique. Increasing concentrations of bovine TSH (0.1, 1, 10, 50 and 1 00 mU/1), with or without tumour necrosis factor-alpha (TNF alpha), in terferon-gamma (IFN gamma) or interleukin-1 alpha (IL-1 alpha) were ad ded to FRTL-5 cells previously deprived of TSH for a minimum of 5 days . RNA was extracted and samples were studied for NIS expression. TSH e nhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0-1 mU/1, reaching a peak at 50 mU/1, an effect detected a fter 6 h of stimulation, but not in the first 2 h. Both TNF alpha and, to a lesser extent, IL-1 alpha inhibited basal and TSH-induced NIS ex pression. High concentrations of IFN gamma also downregulated TSH-stim ulated NIS mRNA expression. Using the same technique, we also investig ated NIS mRNA tissue distribution in two male and one female Wistar ra ts. High levels of NIS expression were detected in the thyroid, stomac h, and mammary gland, lower levels were found in the intestine, adipos e tissue and liver, borderline levels were expressed in the salivary g land, and no expression was detected in the kidneys. In summary, we ha ve shown that TSH upregulates rat NIS gene expression in vitro, and th is induction can be modulated by cytokines. Analysis of the distributi on of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcr iption in different tissue samples.