Kinetics of mononuclear cell infiltration and cytokine expression in iodine-induced thyroiditis in the NOD-H2h4 mouse

Bonita, Raphael; Rose, Noel R.; Rasooly, Linda; Caturegli, Patrizio; Burek, C. Lynne

doi:10.1016/s0014-4800(03)80002-3

Cited by 36 publications

(32 citation statements)

References 30 publications

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“…Thus, the NOD.H2 h4 mouse expresses the thyroiditissusceptible I-A k allele on the NOD background [4]. Both males and females develop thyroiditis in this strain [3,5]. Each experimental group consisted of pooled thyroid cells from B10.A, BALB/c or NOD.H2 h4 mice (n = 7-10) approximately 8-10 weeks of age and from both sexes.…”

Section: Micementioning

confidence: 99%

“…The H-2 k haplotype is associated with a strong immune response to thyroglobulin, a major antigen in AT [4]. Progressive infiltration of mononuclear cells into the thyroid gland and thyroid-specific antibody production is accelerated in NOD.H2 h4 mice upon dietary supplementation with iodine [2,3,5]. Supplementation of iodine to non-susceptible mice such as BALB/c or B10.A mice does not enhance AT, affirming a genetic predilection to autoimmune disease because of the NOD background [6].…”

Section: Introductionmentioning

confidence: 99%

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

Sharma¹,

Traore

Trush

et al. 2008

Clinical and Experimental Immunology

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Section: Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sharma¹,

Traore

Trush

et al. 2008

Clinical and Experimental Immunology

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“…The NOD.H2 h4 strain was developed by backcrossing NOD to B10.A (4R) (4), which possesses the thyroiditis-susceptible I-A k allele (24). Both males and females develop thyroiditis in this strain (6,7). Mice were maintained in conventional (n ϭ 129) or specific pathogen-free (n ϭ 11) housing facilities of the Johns Hopkins School of Medicine.…”

Section: Micementioning

confidence: 99%

“…NOD.H2 h4 mice express the MHC haplotype H-2 k on the NOD background and develop spontaneously AT at a low incidence (4). Incidence can be increased by supplementation of iodine in the diet (5)(6)(7).…”

mentioning

confidence: 99%

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

Sharma¹,

Alegria²,

Talor³

et al. 2005

The Journal of Immunology

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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.

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“…[26] Kimura et al [27] have shown that the local production of IL-12 in the thyroid enhances the expression of sodium-iodide symporter and inhibits thyroid hormonogenesis, thus inducing primary hypothyroidism; also the disease-promoting effect of IL-12 was independent of interferon-g. On the basis of our results and data from experimental models and clinical studies, it may be suggested that the effect of IL-12 on the initiation and regulation of immune responses and also on thyroid function is crucial in HT.…”

Section: Resultsmentioning

confidence: 99%

Impact of IL-10 and IL-12B single nucleotide polymorphisms on circulating cytokine level in development of Hashimoto's thyroiditis

Gerenova

Manolova

Stanilova

2016

Biotechnology & Biotechnological Equipment

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Hashimoto's thyroiditis (HT) is an organ-specific, mainly Th1 autoimmune disorder. New evidence has accumulated for involvement of Treg-produced cytokines. Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with antagonistic effect on Th differentiation. This study was designed to investigate the correlation of circulating IL-10 and IL-12p40 with their genotypes in 124 HT patients in different stages of disease. The IL-10 and IL-12p40 circulating level in the serum of HT patients and healthy controls was determined by enzyme-linked immunosorbent assay. Genotyping for the 3'UTR A/C IL12B polymorphism was performed using restriction fragment length polymorphismÀpolymerase chain reaction and genotyping for ¡1082 A/G by amplification refractory mutation system (ARMS)-PCR. The results showed significantly enhanced IL-12p40 serum quantity both in euthyroid and hypothyroid stages compared to controls and insignificantly decreased level after levothyroxine treatment. Regarding the 3'UTR A/C IL12B polymorphism, a significantly higher frequency of the AA genotype was observed in HT patients than in healthy individuals. The serum IL-10 level was significantly increased in hypothyroid HT patients compared to controls and euthyroid patients. Stratification based on the ¡1082 A/G polymorphism revealed a significantly enhanced level of circulating IL-10 in hypothyroid patients with a GG genotype compared to AA and AG genotypes. There were also significant differences between the circulating IL-10 quantity in hypo-and euthyroid patients with GG genotypes. In conclusion, the IL-12p40 and IL-10 serum level in HT patients was dependent on the genotype and HT stages, suggesting that enhanced IL-10 serum level in combination with enhanced IL-12p40 is associated with hypothyroidism in HT development.

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Kinetics of mononuclear cell infiltration and cytokine expression in iodine-induced thyroiditis in the NOD-H2h4 mouse

Cited by 36 publications

References 30 publications

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

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

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

Impact of IL-10 and IL-12B single nucleotide polymorphisms on circulating cytokine level in development of Hashimoto's thyroiditis

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