Interleukin-1 Beta (IL-1β) Binds to Intact Porcine Thyroid Follicles, Decreases Iodide Uptake but has no Effect on cAMP Formation or Proliferation

Nolte, Andrea; Bechtner, G.; Rafferzeder, M.; Gärtner, Roland

doi:10.1055/s-2007-1001720

Cited by 12 publications

(5 citation statements)

References 22 publications

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“…Upon injection, IL-1␣ and IL-1␤ stimulate thyroid growth in rats (32), and IL-1␣ promotes the growth of a thyroid carcinoma cell line via Ca 2ϩ /calmodulin pathways (33). In contrast, the group of Gärtner found no effect of IL-1␤ on thyrocyte proliferation using a porcine thyroid follicle culture system (34). IL-6 was described as not affecting basal cell proliferation of FRTL-5 cells, it stimulated DNA-synthesis in a dose-dependent manner in the presence of TSH (35).…”

Section: Discussionmentioning

confidence: 99%

Antigen-Presenting Dendritic Cells as Regulators of the Growth of Thyrocytes: A Role of Interleukin-1 and Interleukin-6

Simons¹

1998

Endocrinology

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An accumulation of antigen-presenting dendritic cells (DC) in the thyroid gland, followed by thyroid autoimmune reactivity, occurs in normal Wistar rats during iodine deficiency, and spontaneously in diabetic-prone Biobreeding rats. This intrathyroidal DC accumulation coincides with an enhanced growth rate and metabolism of the thyrocytes, suggesting that both phenomena are related. Because DC are known to regulate the hormone synthesis and growth in other endocrine systems (i.e. the pituitary, the ovary, and the testis), we tested the hypothesis that DC, known for their superb accessory cell function in T cell stimulation, act as regulators of thyrocyte proliferation (and hormone secretion).We investigated the effect of (Nycodenz density gradient) purified splenic DC from Wistar rats on the growth rate of and thyroid hormone secretion by Wistar thyroid follicles (collagenase dispersion) in culture. Various numbers of DC and follicles were cocultured during 24 h. The proliferative capacity of thyrocytes was measured by adding tritiated thymidine ( 3 H-TdR) and bromodeoxyuridine, the hormone secretion into the culture fluid was measured by using a conventional T 3 RIA. Furthermore, antibodies directed against interleukin-1␤ (IL-1␤), IL-6, and tumor necrosis factor-␣ (TNF-␣) were added to these cocultures to determine the role of these cytokines in a possible DC regulation of thyrocyte growth. Cocultures were also carried out in the presence of antimajor histocompatibility complex-class I (MHC I), anti-MHC II, antiintercellular adhesion molecule-1 (ICAM-1), and antilymphocyte function-associated antigen-1␣ (LFA-1␣) antibodies to possibly interfere with DC-thyrocyte interactions.The addition of DC to thyroid follicles clearly inhibited their 3 HTdR uptake, particularly at a 10:1 ratio, in comparison to follicle cultures alone, both under basal conditions and after TSH stimulation (75 Ϯ 7% and 49 Ϯ 11% reduction, respectively, n ϭ 4). The follicle T 3 secretion (after TSH stimulation) was also suppressed by DC in this system, but to a lesser extent (at best at an 1:1 ratio, 25 Ϯ 7% reduction, n ϭ 4). The DC-induced inhibition of thyroid follicle growth was totally abrogated after addition of anti-IL-1␤ antibodies; anti-IL-6 only had effect on the DC inhibition of non-TSH-stimulated thyrocytes, whereas anti-TNF-␣ demonstrated no effect at all. The antibodies to MHC and to adhesion molecules had also no effect on this DC-induced growth inhibition. The effect of the different anticytokine and anti-adhesion antibodies on the T 3 secretion from thyroid follicles was not investigated.The clear inhibition of thyrocyte growth by splenic DC (classical antigen-presenting cells) again demonstrates the regulatory role of DC in endocrine systems. Proinflammatory cytokines such as IL-1␤ and IL-6 are important mediators in this regulation. The here shown dual role of DC represents a link between the immune and endocrine system, which may form the gateway to the understanding of the initiation of thyroid autoimmune reaction...

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Section: Discussionmentioning

confidence: 99%

Antigen-Presenting Dendritic Cells as Regulators of the Growth of Thyrocytes: A Role of Interleukin-1 and Interleukin-6

Simons¹

1998

Endocrinology

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“…The role of cAMP in IL-1 signal transduction is variable. Al though in some biological systems IL-1 in creases the level of cytosolic cAMP [18], in some cells IL-1 does not change cAMP levels [19][20][21] or may decrease them [22], In some cases, cAMP modulates or mimics effects of IL-1 [23,24], without mediating them. How ever, other effects of IL-1 seem to be indepen dent of cAMP [25,26], cAMP and IL-1 may even have opposing effects; thus, in human lung fibroblasts cAMP inhibits IL-l-induced IL-6 production [27], In the present study IL-1 had no detectable effect on the concentra tion SP-B mRNA, whereas cAMP significant ly increased SP-B mRNA.…”

Section: Discussionmentioning

confidence: 99%

lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

et al. 1997

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Interleukin-1 (IL-1) is an important participant in infectious and inflammatory conditions. Interleukin-1 receptor antagonist (IL-1 ra) prevents the effect of IL-1. We have shown that injection of interleukin-1 α (IL-1α) into the amniotic fluid of pregnant rabbits stimulates the expression of surfactant protein-A (SP-A) in the lungs of the fetuses. We hypothesized that IL-1α similarly enhances the expression of SP-A in rabbit lung explants in vitro. Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth’s medium on a rotating platform in the presence or absence of IL-1α (5.7–570 ng/ml) or IL-Ira (1–10 μg/ml). Dibutyryl cAMP (1 mM) served as a positive control. After 3 days in culture, the explants were harvested and Northern analysis of SP-A was performed using the 1.9-kb rabbit SP-A cDNA probe. IL-1α and dibutyryl cAMP increased the expression of SP-A twofold, as judged by video densitometry. IL-1ra did not change SP-A expression as compared with controls, suggesting that endogenous IL-1 activity was not responsible for the basal level of SP-A expression in the explants. Dibutyryl cAMP increased the expression of SP-B mRNA, whereas IL-1 α had no effect on SP-B mRNA concentration. We conclude that inflammatory mediators interact with lung cells to alter synthesis of important components of the surfactant system.

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“…Thyroid peroxidase (TPO) mRNA expression and protein content, important for the oxidation of iodide to iodine, is also directly affected by IL1 in human thyrocytes and rat thyroid FTRL-5 cells (Asakawa et al 1996, Gerard et al 2006. Moreover, IL1b impairs basal and TSH-stimulated uptake of iodide by the natrium/iodide symporter (NIS) in porcine thyroid follicles (Nolte et al 1994). The role of IL6 is less well established: one study showed that IL6 inhibits the TSHand cAMP-induced increase in TPO mRNA expression and T 3 secretion in thyrocytes obtained from Graves' disease patients (Tominaga et al 1991), while IL6 has only a minor effect on cultured human thyroid cells (Rasmussen et al 1991).…”

Section: The Effect Of Cytokines On Th Synthesismentioning

confidence: 99%

The molecular basis of the non-thyroidal illness syndrome

Vries¹,

Fliers²,

Boelen³

2015

Journal of Endocrinology

152

116

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The 'sick euthyroid syndrome' or 'non-thyroidal illness syndrome' (NTIS) occurs in a large proportion of hospitalized patients and comprises a variety of alterations in the hypothalamus-pituitary-thyroid (HPT) axis that are observed during illness. One of the hallmarks of NTIS is decreased thyroid hormone (TH) serum concentrations, often viewed as an adaptive mechanism to save energy. Downregulation of hypophysiotropic TRH neurons in the paraventricular nucleus of the hypothalamus and of TSH production in the pituitary gland points to disturbed negative feedback regulation during illness. In addition to these alterations in the central component of the HPT axis, changes in TH metabolism occur in a variety of TH target tissues during NTIS, dependent on the timing, nature and severity of the illness. Cytokines, released during illness, are known to affect a variety of genes involved in TH metabolism and are therefore considered a major determinant of NTIS. The availability of in vivo and in vitro models for NTIS has elucidated part of the mechanisms involved in the sometimes paradoxical changes in the HPT axis and TH responsive tissues. However, the pathogenesis of NTIS is still incompletely understood. This review focusses on the molecular mechanisms involved in the tissue changes in TH metabolism and discusses the gaps that still require further research.

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Interleukin-1 Beta (IL-1β) Binds to Intact Porcine Thyroid Follicles, Decreases Iodide Uptake but has no Effect on cAMP Formation or Proliferation

Cited by 12 publications

References 22 publications

Antigen-Presenting Dendritic Cells as Regulators of the Growth of Thyrocytes: A Role of Interleukin-1 and Interleukin-6

Antigen-Presenting Dendritic Cells as Regulators of the Growth of Thyrocytes: A Role of Interleukin-1 and Interleukin-6

lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

The molecular basis of the non-thyroidal illness syndrome

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