Iodine and IFN-γ Synergistically Enhance Intercellular Adhesion Molecule 1 Expression on NOD.H2h4 Mouse Thyrocytes

Abstract

NOD.H2h4 mice spontaneously develop autoimmune lymphocytic thyroiditis that mimics human Hashimoto’s thyroiditis, a disease where iodine, IFN-γ, and adhesion molecules have all been implicated in the pathogenesis. To study how iodine and IFN-γ modulate the expression of ICAM-1, we analyzed NOD.H2h4 thyrocytes in baseline conditions (day 0) and at several time points following supplementation of iodine in the drinking water. On day 0, a small percentage (∼10%) of thyrocytes constitutively expressed ICAM-1. The expression gradually increased to 13, 25, and 41% on days 7, 14 and 28, respectively, returning to baseline (9%) on day 35. The initial ICAM-1 kinetics was paralleled by thyroidal infiltration of CD45+ hemopoietic cells, which increased from an average of 4% on day 0 to an average of 13, 21, and 24% on days 14, 28, and 35, respectively. To distinguish whether the observed ICAM-1 increase was a direct effect of iodine or a consequence of the immune infiltrate, we treated mouse primary thyrocyte cultures with 0.01 mM sodium iodine and showed a 3-fold increased ICAM-1 expression. To assess interaction between IFN-γ and iodine, we analyzed CD45 and ICAM-1expression on thyrocytes from NOD.H2h4 wild-type and NOD.H2h4 thyr-IFN-γ transgenic littermates. Strikingly, IFN-γ interacted synergistically with iodine to enhance ICAM-1 expression on thyrocytes. These findings suggest that iodine and IFN-γ cooperate to promote thyroidal expression of ICAM-1 in this mouse model of thyroiditis, highlighting the complex interplay present in the pathogenesis of Hashimoto’s thyroiditis.

More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels

“…Secondly, iodine has a toxic effect on thyroid cells (51)(52)(53). Thirdly, iodine directly stimulates immune and immunity-related cells (54)(55)(56). Then what is the upper limit of iodine intake that could be considered a risk factor for iodine-induced autoimmune thyroiditis in humans?…”

Intracellular adhesion molecule-1 up-regulation on thyrocytes by iodine of non-obese diabetic.H2h4 mice is reactive oxygen species-dependent

“…We have reported previously that NOD.H2 h4 mice express intracellular adhesion molecule-1 (ICAM-1) on their thyrocytes constitutively, and that iodine supplementation in their drinking water up-regulated this ICAM-1 expression [6,7]. In vitro iodine treatment of isolated thyroid follicular cells also demonstrated enhanced expression of ICAM-1 on their surface [6].…”

Molecular parameters linking thyroglobulin iodination with autoimmune thyroiditis

“…[68][69][70][71] However, events that occur when iodide is administered to iodopenic hosts may not necessarily reflect intrathyroidal changes occurring in euthyroid individuals on an iodide-rich diet (>500 g I/day). In this regard, work by Burek's laboratory has shown that the constitutive expression of the intracellular adhesion molecule-1 (ICAM-1) on thyrocytes of NOD.H2h4 mice is upregulated by iodine supplementation of drinking water, 72,73 with concomitant increase in E-selectin and VCAM-1 expression on intrathyroidal endothelial cells. 72 These events may promote the homing of autoreactive lymphocytes in the thyroid gland.…”