Overexpression of Immediate Early Genes in Active Graves’ Ophthalmopathy

Lantz, Mikael; Vondrichova, Tereza; Parikh, Hemang; Frenander, Christofer; Ridderstråle, Martin; Åsman, Peter; Åberg, Magnus; Groop, Leif; Hallengren, Bengt

doi:10.1210/jc.2004-2275

Cited by 64 publications

(60 citation statements)

References 35 publications

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“…There is evidence of overexpression of mature adipocyterelated genes such as leptin, adiponectin and PPAR g and cysteine-rich angiogenic inducer 61 in TAO compared with normal orbital tissue samples (29,30). This supports the concept that de novo adipogenesis occurs within the orbit in active TAO.…”

Section: Discussionsupporting

confidence: 64%

The effects of tumour necrosis factor-α and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis

Cawood

Moriarty²,

O’Farrelly³

et al. 2006

eur j endocrinol

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Objective: Cytokines are likely to play a key pathogenic role in thyroid-associated ophthalmopathy (TAO). Anti-cytokine therapy has been proposed to be a possible treatment for active TAO. We aimed to establish the effects of selected cytokines on intercellular adhesion molecule 1 (ICAM1) expression, glycosaminoglycan (GAG) production and adipogenesis in orbital fibroblasts (OFs) from patients with TAO. Methods: Orbital tissue was taken during surgery from eight patients with TAO and five control subjects. OFs were cultured and ICAM1 expression measured by flow cytometry. GAG production was measured by hyaluronic acid ELISA. OFs were grown in adipogenic media and the degree of adipogenesis quantified. Results: Responses were similar in OFs from patients with and without TAO. Tumour necrosis factor-a (TNFa) and interleukin1 (IL1) (0.1 ng/ml) stimulated ICAM1 expression by eight-to ten-fold. Anticytokine agents inhibited the cytokine-upregulated ICAM1 expression by 90-99% (P!0.01). TNFa and IL1 (0.1 ng/ml) increased hyaluronic acid production by 44 and 95% (P!0.01) respectively. Anti-cytokine agents inhibited these responses by 79-138% (P!0.04). TNFa (0.1 ng/ml) inhibited adipogenesis (K0.013 AU and K1.0; P!0.03) whilst IL1 (0.1 ng/ml) stimulated adipogenesis (C0.05 AU and C5.7; P!0.02) measured by oil-red-O extraction and visual assessment respectively. The anti-IL1 agent inhibited IL1-mediated adipogenesis by 69-106% (P!0.04). Conclusion: TNFa and IL1 stimulate ICAM1 expression and GAG production, but have opposite effects on adipogenesis in OFs in vitro. IL1 promotes adipogenesis and its effects can be blocked by anti-IL1 agents in vitro. These agents may be the anti-cytokine treatment of choice for clinical trials in active TAO. European Journal of Endocrinology 155 395-403

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Section: Discussionsupporting

confidence: 64%

The effects of tumour necrosis factor-α and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis

Cawood

Moriarty²,

O’Farrelly³

et al. 2006

eur j endocrinol

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“…However, previous studies have also implicated Cyr61 in the pathogenesis of inflammatory diseases, such as atherosclerosis (9), inflammatory cardiomyopathy (10), and Graves' ophthalmopathy (11). In a rat model of bacteria-induced apical periodontitis, we found that osteoblastic expression of Cyr61 correlates with the severity of inflammation-associated bone loss (12).…”

mentioning

confidence: 60%

Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

Kok

Hou

Hong

et al. 2011

Arthritis & Rheumatism

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Objective. To examine the effects of proinflammatory cytokines on Cyr61 expression in osteoblastic cells and the modulatory action of simvastatin, to assess the role of CREB in Cyr61 induction, and to investigate the relationship of osteoblastic expression of Cyr61 to disease progression in experimental arthritis.Methods. Cyr61 expression and CREB phosphorylation at serine 133 were examined by Western blotting. Promoter activity of Cyr61 was assessed by luciferase assay with promoter deletion/mutagenesis and forced expression/gene silencing of CREB. Interaction between CREB and the Cyr61 promoter was evaluated by electrophoretic mobility shift assay and chromatin immunoprecipitation. CCL2 expression was examined by Northern blotting and enzyme-linked immunosorbent assay. In rats with collagen-induced arthritis (CIA), osteoblastic expression of Cyr61 was examined by immunohistochemistry, and disease progression was assessed by clinical, radiographic, and histologic examination. Results. In primary human osteoblasts and U2OS

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“…Overexpression of adipocyte-related immediate early genes in active ophthalmopathy and cysteine-rich, angiogenic inducer 61 (CYR61) may have a role in both orbital inflammation and adipogenesis and serve as a marker of disease activity [28].…”

Section: Excess Subcutaneous Adiposity and Chronic Lymphedemamentioning

confidence: 99%

Liposuction Normalizes – in Contrast to Other Therapies – Lymphedema-Induced Adipose Tissue Hypertrophy

Brorson

2013

Handchir Mikrochir plast Chir

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The various types of treatment of lymphedema are under discussion and there has been some controversy regarding liposuction for lymphedema. Although it is clear that conservative therapies such as complex decongestive therapy (CDT) and controlled compression therapy (CCT) should be tried in the first instance, options for the treatment of late-stage lymphedema that is not responding to such treatment is not so clear. Improvements in technique, patient preparation, and patient follow-up have led to a greater and a wider acceptance of liposuction as a treatment for lymphedema. This paper outlines the benefits of using liposuction and presents the evidence to support its use.

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Overexpression of Immediate Early Genes in Active Graves’ Ophthalmopathy

Cited by 64 publications

References 35 publications

The effects of tumour necrosis factor-α and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis

The effects of tumour necrosis factor-α and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis

Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

Liposuction Normalizes – in Contrast to Other Therapies – Lymphedema-Induced Adipose Tissue Hypertrophy

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