Autor: |
Sharma, R., Traore, K., Trush, M. A., Rose, N. R., Burek, C. Lynne |
Předmět: |
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Zdroj: |
Clinical & Experimental Immunology; Apr2008, Vol. 152 Issue 1, p13-20, 8p, 1 Black and White Photograph, 1 Diagram, 3 Graphs |
Abstrakt: |
Intracellular adhesion molecule-1 (ICAM-1) expression on the thyroid follicular cells of non-obese diabetic (NOD).H2h4 mice is enhanced by iodide treatment, which correlates with autoimmune thyroid disease in genetically susceptible NOD.H2h4 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.H2h4 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.H2h4 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.H2h4 mice prior to iodine treatment. No such expression was found in BALB/c mice. Treatment of NOD.H2h4 thyroid cells with diphenyleneiodium, an inhibitor of NADPH oxidase, reduced generation of ROS and of ICAM-1 protein expression. Thus, thyrocytes from NOD.H2h4 mice produce enhanced levels of ROS that may be mediated by NADPH oxidase. Consequently, in NOD.H2h4 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. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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