Influence of iodide excess and interferon-gamma on human primary thyroid cell proliferation, thyroglobulin secretion, and intracellular adhesion molecule-1 and human leukocyte antigen-DR expression.
BACKGROUND
The effect of iodide on thyroid cell proliferation and function in vivo or in cultured thyroid cells has been previously reported and is still controversial. The aim of this study was to clarify these conflicting results by examining if prolonged high iodide exposition with or without interferon (IFN)-gamma has an effect on human primary thyroid cell proliferation, thyroglobulin (Tg) production, and intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen (HLA)-DR expression.


METHODS
Primary human thyroid cells were used. Cells were cultured in Coon's modified Ham's F-12 medium supplemented with 5% fetal calf serum in monolayer conditions to induce proliferation and were aggregated for molecular expression and Tg production analysis. HLA-DR and ICAM-1 expression were measured by flow cytometry and Tg by immunometric assay.


RESULTS
Potassium iodide (KI) was more potent in arresting primary human thyroid cell proliferation as compared to sodium iodide and the effect was mediated by its action at G0/G1 and G2/M phases of the cell cycle. There were no signs of apoptosis or necrosis. An excess of KI alone did not change the expression of HLA-DR and Tg production, but gradually increased ICAM-1. Low-dose IFN-gamma and excess KI in combination transiently inhibited HLA-DR expression, while ICAM-1 was expressed at a higher level than with IFN-gamma alone. Tg production was moderately increased with low-dose IFN-gamma. However, a combination of high-dose KI with low-dose IFN-gamma significantly decreased Tg secretion, compared with IFN-gamma alone.


CONCLUSIONS
Augmented ICAM-1 in the presence of iodide excess and low-dose IFN-gamma could induce secretion of proinflammatory cytokines and lymphocytic infiltration in the thyroid gland. Decreased Tg production in the presence of KI excess and IFN-gamma could explain the development of hypothyroidism after adding iodide in a diet of subjects that already have lymphocytic infiltration and/or mild inflammation in the thyroid gland.
Kostic
Irena
I
Institute of Pathophysiology, School of Medicine, University of Kragujevac, Kragujevac, Serbia.
Toffoletto
Barbara
B
Fontanini
Elisabetta
E
Moretti
Massimo
M
Cesselli
Daniela
D
Beltrami
Carlo A
CA
Ambesi Impiombato
Francesco S
FS
Curcio
Francesco
F
D017304:Annexin A5 / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D007454:Iodides / Q000494:pharmacology*; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects
D017304:Annexin A5; D004273:DNA, Neoplasm; D006684:HLA-DR Antigens; D007454:Iodides; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013954:Thyroglobulin