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

R. Sharma, K. Traore, M. A. Trush, N. R. Rose, C. Lynne Burek

Research output: Contribution to journalArticlepeer-review

Abstract

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, p67phox, 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.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalClinical and Experimental Immunology
Volume152
Issue number1
DOIs
StatePublished - Apr 2008

Keywords

  • Adhesion molecules
  • Autoimmunity
  • Gene regulation
  • Rodent

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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