Interleukin-6 Stimulates Thyrotropin Receptor Expression in Human Orbital Preadipocyte Fibroblasts from Patients with Graves' Ophthalmopathy

Jyonouchi, Soma; Valyasevi, Rosanee W.; Harteneck, Debra A.; Dutton, Charyl M.; Bahn, Rebecca S.

doi:10.1089/105072501753210984

Cited by 83 publications

(54 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If hyperthyroidism per se does not trigger differentiation, it could be caused by inflammatory or autoimmune processes. Recent reports have suggested that interleukin-6 may be implicated (Jyonouchi et al 2001) but since in vitro manipulation can alter TSHR expression it seems that in vivo experiments will be required to resolve this issue.…”

Section: Discussionmentioning

confidence: 99%

Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo

Starkey¹,

Janezić²,

Jones³

et al. 2003

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The thyrotrophin receptor (TSHR) provides an autoantigenic link between the thyroid and orbit in Graves' (GD) and thyroid eye diseases (TED). We measured TSHR transcripts in different fat depots to determine whether TSHR expression levels are influenced by the autoimmune/inflammatory process and/or thyroid hormone status, using quantitative real-time PCR. Nine intact or fractionated adipose samples, from patients with GD and/or TED, were analysed ex vivo. Eight expressed the TSHR, at levels approaching the thyroid, and one was at the limit of detection. Thirteen/fifteen orbital and abdominal fat samples from patients free of GD and TED, measured ex vivo, were negative for TSHR transcripts and two were at the limit of detection. All preadipocyte samples induced to differentiate in vitro expressed the TSHR. To investigate the influence of thyroid hormone status on adipose TSHR expression, we induced hyper-and hypothyroidism in BALBc mice by administering tri-iodothyronine and propylthiouracil respectively. In euthyroid animals, whole fat samples were at the limit of detection and were not altered by thyroid hormone status. The results show that adipose TSHR expression ex vivo indicates adipogenesis in progress in vivo and is associated with the autoimmune/inflammatory process in GD and TED but is not restricted to the orbit or influenced by thyroid hormone status.

show abstract

Section: Discussionmentioning

confidence: 99%

Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo

Starkey¹,

Janezić²,

Jones³

et al. 2003

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…Subsequent passage of these cells resulted in the loss of TSHr expression. The authors concluded that the expression of this receptor in TAO may be induced in vivo by a humoral factor not present in the cell culture environment (12,13). Recently, gene expression profiles in extraocular muscles in adult mice by high-density oligonucleotide arrays were analyzed (18).…”

Section: Discussionmentioning

confidence: 99%

Real-time PCR provides evidence for thyrotropin receptor mRNA expression in orbital as well as in extraorbital tissues

Agretti

Chiovato

Marco

et al. 2002

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: The TSH receptor (TSHr) expressed on thyroid follicular cells is the autoantigen involved in the pathogenesis of Graves' hyperthyroidism. Whether this receptor is expressed in extrathyroidal tissues, and whether it participates directly in the pathogenesis of thyroid-associated ophthalmopathy (TAO) is unclear. Design: The aim of the present study was to measure TSHr mRNA in retro-orbital tissues, retro-orbital adipose tissue, extraocular muscle, and skin from patients with TAO and in several tissues from patients not affected by thyroid diseases using RT-PCR and real-time PCR. Methods: Total RNA was isolated from tissue specimens, reverse transcribed, and amplified using specific primers for the extracellular portion and a part of a 1.3 kbp variant form of the TSHr gene. Determination of TSHr mRNA levels using real-time PCR was also performed by the TaqMan system; to normalize for differences in the amount of total RNA added to the reaction, amplification of b-actin gene was performed as an endogenous control. Results: A single-round RT-PCR amplification using specific primers for the extracellular portion of the TSHr gene demonstrated an amplification product of 1.2 kbp in the thyroid, but not in all other tissues. A second-round RT-PCR amplification using the same primers and starting from the previous amplification product demonstrated a band of the size expected for the TSHr gene in all tissue specimens analyzed irrespective of their origin. Similar results were obtained using primers specific for a part of the variant form of 1.3 kbp of the TSHr gene. The amount of TSHr mRNA measured by real-time PCR with the TaqMan probe and expressed as TSHr/b-actin ratio was similar in the tissues from TAO patients with respect to the tissues from subjects not affected by thyroid diseases. Conclusions: We measured TSHr mRNA in tissues from patients with TAO using the very sensitive and quantitative method of real-time PCR. The level of transcription was similar to that measured in extraorbital tissues from patients who were not affected by thyroid diseases. These data suggest an illegitimate TSHr mRNA transcription in all the tissues examined apart from thyroid.

show abstract

“…This leads to excessive production of the cytokines: IL-1α, IL-1β, IL-6, IL-8, macrophage chemoattractant protein (MCP-1) and transforming growth factor-β (TGF-β) [19,20]. IL-6 increases immunoglobulin production, β-cells differentiation and enhances thyrotropin receptor (TSHR) expression on the fibroblast surface [21]. Previous studies revealed that thyrotropin receptor is the main autoantigen in TAO in patients with Graves' disease [22].…”

Section: Pathogenesis Of Thyroid-associated Ophthalmopathymentioning

confidence: 99%

An update on thyroid-associated ophthalmopathy in children and adolescents

Szczapa-Jagustyn¹,

Gotz‐Więckowska²,

Kocięcki³

2016

Journal of Pediatric Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

Interleukin-6 Stimulates Thyrotropin Receptor Expression in Human Orbital Preadipocyte Fibroblasts from Patients with Graves' Ophthalmopathy

Cited by 83 publications

References 25 publications

Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo

Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo

Real-time PCR provides evidence for thyrotropin receptor mRNA expression in orbital as well as in extraorbital tissues

An update on thyroid-associated ophthalmopathy in children and adolescents

Contact Info

Product

Resources

About