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Title: Intracellular adhesion molecule-1 up-regulation on thyrocytes by iodine of non-obese diabetic.H2(h4) mice is reactive oxygen species-dependent.

Authors: Sharma, R; Traore, K; Trush, M A; Rose, N R; Burek, C Lynne

Published In Clin Exp Immunol, (2008 Apr)

Abstract: Intracellular adhesion molecule-1 (ICAM-1) expression on the thyroid follicular cells of non-obese diabetic (NOD).H2(h4) mice is enhanced by iodide treatment, which correlates with autoimmune thyroid disease in genetically susceptible NOD.H2(h4) mice. The current study examines the mechanism of iodine-enhanced up-regulation of ICAM-1 on the surface of thyroid cells. We hypothesized that the up-regulation of ICAM-1 is due to a transient increase in production of reactive oxygen species (ROS). ROS may initiate signalling of the ICAM-1 gene promoter, enhancing up-regulated ICAM-1 protein on the cell surface. Single-cell suspensions of thyroid follicular cells from thyroiditis-susceptible NOD.H2(h4) or non-susceptible BALB/c mice were treated in vitro with sodium iodide. Extracellular and intracellular ROS were assessed by luminol-derived chemiluminescence and flow cytometry assays respectively. Our results demonstrate that thyroid follicular cells of NOD.H2(h4) generate higher levels of ROS compared with cells from non-susceptible strains of mice. Expression of a subunit protein of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p67(phox), was analysed by Western blot immunoassay. A constitutive expression of the p67(phox) subunit protein was observed in NOD.H2(h4) mice prior to iodine treatment. No such expression was found in BALB/c mice. Treatment of NOD.H2(h4) thyroid cells with diphenyleneiodium, an inhibitor of NADPH oxidase, reduced generation of ROS and of ICAM-1 protein expression. Thus, thyrocytes from NOD.H2(h4) mice produce enhanced levels of ROS that may be mediated by NADPH oxidase. Consequently, in NOD.H2(h4) mice the ROS-induced signal for ICAM-1 up-regulation may contribute to mononuclear cellular infiltration of the thyroid gland and the progression of autoimmune thyroid disease.

PubMed ID: 18241232 Exiting the NIEHS site

MeSH Terms: Animals; Cells, Cultured; Diabetes Mellitus, Type 1/metabolism*; Enzyme Inhibitors/pharmacology; Female; Intercellular Adhesion Molecule-1/metabolism*; Male; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Nitric Oxide Synthase/antagonists & inhibitors; Onium Compounds/pharmacology; Phosphoproteins/metabolism; Reactive Oxygen Species/metabolism*; Sodium Iodide/pharmacology*; Thyroid Gland/drug effects; Thyroid Gland/metabolism*; Thyroiditis, Autoimmune/metabolism; Up-Regulation/drug effects

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