Iodine and IFN-gamma synergistically enhance intercellular adhesion molecule 1 expression on NOD.H2h4 mouse thyrocytes.
NOD.H2(h4) mice spontaneously develop autoimmune lymphocytic thyroiditis that mimics human Hashimoto's thyroiditis, a disease where iodine, IFN-gamma, and adhesion molecules have all been implicated in the pathogenesis. To study how iodine and IFN-gamma modulate the expression of ICAM-1, we analyzed NOD.H2(h4) 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 ( approximately 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-gamma and iodine, we analyzed CD45 and ICAM-1expression on thyrocytes from NOD.H2(h4) wild-type and NOD.H2(h4) thyr-IFN-gamma transgenic littermates. Strikingly, IFN-gamma interacted synergistically with iodine to enhance ICAM-1 expression on thyrocytes. These findings suggest that iodine and IFN-gamma 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.
Sharma
Rajni B
RB
Department of Pathology, School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Alegria
Judy D
JD
Talor
Monica V
MV
Rose
Noel R
NR
Caturegli
Patrizio
P
Burek
C Lynne
CL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006799:Housing, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D012974:Sodium Iodide / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013045:Species Specificity; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D012974:Sodium Iodide