Graves' IgG activate upstream enhancer of the sodium/iodide symporter.
Graves' thyroid tissue has been shown to express elevated levels of human sodium/iodide symporter (hNIS) mRNA and protein. In the present work, we demonstrate for the first time that hNIS gene expression in Graves' disease (GD) is up-regulated by Graves' IgG. Here, in transient transfection experiments using FRTL-5 cells, hNIS promoter and enhancer/luciferase construct showed an up to six-fold increase in transcriptional activity after incubation with purified Graves' IgG. Mutation of a CRE site in hNIS enhancer inhibited Graves' IgG response. In addition, mutation of a novel putative regulatory region in hNIS promoter reduced the stimulation three-fold. This discovered putative regulatory sequence might play a role in hNIS up-regulation by Graves' IgG and TSH. The data presented here complement our current knowledge of the pathogenesis of GD and will contribute to a better understanding of mechanisms regulating the thyroid iodide concentrating activity.
Breous
Ekaterina
E
Abteilung Innere Medizin I, Universität Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
Wenzel
Achim
A
Loos
Ulrich
U
D000818:Animals; D002460:Cell Line; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D006111:Graves Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D027981:Symporters / Q000235:genetics*; D013972:Thyrotropin / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D000099209:Sodium-Iodide Symporters
D007074:Immunoglobulin G; D027981:Symporters; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters