Dexamethasone regulation of glycosaminoglycan synthesis in cultured human skin fibroblasts. Similar effects of glucocorticoid and thyroid hormones.

Smith, Terry J.

doi:10.1172/jci111642

Cited by 98 publications

(48 citation statements)

References 42 publications

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“…The drug is often effective on GO owing to its antiinflammatory and immunosuppressive actions, including interference with the function of T and B lymphocytes, reduction in the recruitment of neutrophils, monocytes, and macrophages in the inflamed area, inhibition of the function of immunocompetent cells, and inhibition of the release of mediators, including cytokines (108). In addition, glucocorticoids decrease GAG synthesis and secretion by orbital fibroblasts (109,110).…”

Section: Management Of Severe Graves' Ophthalmopathymentioning

confidence: 99%

Management of Graves' Ophthalmopathy: Reality and Perspectives

Bartalena¹

2000

Endocrine Reviews

299

351

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Graves' ophthalmopathy is an debilitating disease impairing the quality of life of affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not satisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal taping of the eyes, prisms) can control symptoms and signs. In severe forms of the disease (3-5%), aggressive measures are required. If the disease is active, high-dose glucocorticoids and/or orbital radiotherapy, or orbital decompression represent the mainstay of treatment. If the disease is severe but inactive, orbital decompression is preferred. Novel treatments such as somatostatin analogs or intravenous immunoglobulins are under evaluation. Rehabilitative (extraocular muscle or eyelid) surgery is often needed after treatment and inactivation of eye disease. Correction of both hyper-and hypothyroidism is crucial for the ophthalmopathy. Antithyroid drugs and thyroidectomy do not influence the course of the ophthalmopathy, whereas radioiodine treatment may cause the progression of preexisting ophthalmopathy, especially in smokers. The exacerbation, however, is prevented by glucocorticoids. In addition, thyroid ablation may prove beneficial for the ophthalmopathy in view of the pathogenetic model relating eye disease to autoimmune reactions directed against antigens shared by the thyroid and the orbit.

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Section: Management Of Severe Graves' Ophthalmopathymentioning

confidence: 99%

Management of Graves' Ophthalmopathy: Reality and Perspectives

Bartalena¹

2000

Endocrine Reviews

299

351

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“…Some of the culture strains were kindly provided by Dr. R. Bahn (Mayo Clinic, Rochester, MN). Fibroblast monolayers were covered with Eagle's medium supplemented with 10% FBS, antibiotics, and glutamine as described previously (48). Cultures were incubated in a 37°C, humidified, 5% CO 2 atmosphere and were serially passaged with gentle treatment with trypsin/EDTA.…”

Section: Cell Culture Serum Collection and Igg Preparationmentioning

confidence: 99%

Igs from Patients with Graves’ Disease Induce the Expression of T Cell Chemoattractants in Their Fibroblasts

Pritchard

Horst

Cruikshank

et al. 2002

The Journal of Immunology

157

143

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Thyroid-associated ophthalmopathy and dermopathy are connective tissue manifestations of Graves’ disease (GD). Tissue remodeling is a prominent feature of both and is apparently driven by recruited T cells. In this study, we report that IgG isolated from patients with GD (GD-IgG) up-regulates T lymphocyte chemoattractant activity in GD-derived fibroblasts from orbit, thyroid, and several regions of skin. This chemoattractant activity, absent in fibroblasts from donors without known thyroid disease, is partially susceptible to neutralization by anti-IL-16 and anti-RANTES Abs. IL-16 is a CD4+-specific chemoattractant and RANTES is a C-C-type chemokine. IL-16 and RANTES protein levels, as determined by specific ELISAs, are substantially increased by GD-IgG in GD fibroblasts. Addition of the macrolide, rapamycin, to fibroblast culture medium blocked the up-regulation by GD-IgG of IL-16, implicating the FRAP/mTOR/p70s6k pathway in the induction of IL-16 expression. These findings suggest a specific mechanism for activation of fibroblasts in GD resulting in the recruitment of T cells. They may provide insight into a missing link between the glandular and extrathyroidal manifestations of GD.

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“…Substantial evidence supports the concept that fibroblasts from different anatomic regions exhibit distinct phenotypes in culture. Characteristic expression patterns of receptors (15), gangliosides (16,17), glycosaminoglycans (17)(18)(19)(20)(21)(22), plasminogen activator inhibitor type 1 (23)(24)(25)(26), and PG endoperoxide H synthase-2 (27) have recently been documented in different populations of fibroblasts. Moreover, fibroblasts are capable of responding to their microenvironment in a complex manner.…”

Section: Cd8mentioning

confidence: 99%

“…Procedures for the culture of primary human fibroblasts have been published previously (19). Briefly, orbital fibroblasts were obtained from individuals undergoing transantral decompressive surgery for severe thyroidassociated ophthalmopathy (TAO) or for some other condition where normal orbital connective tissue was removed.…”

Section: Cell Culturementioning

confidence: 99%

Cultured Human Fibroblasts Express Constitutive IL-16 mRNA: Cytokine Induction of Active IL-16 Protein Synthesis Through a Caspase-3-Dependent Mechanism

Sciaky

Brazer

Center

et al. 2000

The Journal of Immunology

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Human fibroblasts can express numerous regulatory molecules that influence immune function. IL-16, a ligand for CD4, is a chemoattractant molecule expressed by lymphocytes, eosinophils, mast cells, and lung epithelium. It appears that the sole target for IL-16 is the CD4-bearing cell. Here we demonstrate that fibroblasts from several tissues can express IL-16 mRNA and protein as well as IL-16-dependent chemoattractant activity. The transcript is expressed abundantly under basal culture conditions as a 2.5-kb band on Northern analysis, similar to that observed in lymphocytes. IL-16 protein and activity are undetectable in fibroblast cultures under these same control conditions. However, when treated with proinflammatory cytokines such as IL-1β, they express very high levels of IL-16 protein and chemoattractant activity, a substantial component of which can be blocked with IL-16-neutralizing Abs. The amount of IL-16 protein released into the medium is 3- to 4-fold greater, on a per cell basis, than that observed in lymphocytes. The induction of IL-16 protein by IL-1β can be attenuated with specific inhibition of caspase-3, which could be detected in IL-1β-treated fibroblasts. IL-1β also induces RANTES mRNA, protein, and activity, and most of the chemoattractant activity released from fibroblasts not derived from IL-16 can be attributed to RANTES. Human fibroblasts appear to be an important source of IL-16 and through expression of this molecule may have key roles in the recruitment of CD4+ cells to sites of inflammation. IL-16 expression and the mechanism involved in its regulation appear to be cell type specific.

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Dexamethasone regulation of glycosaminoglycan synthesis in cultured human skin fibroblasts. Similar effects of glucocorticoid and thyroid hormones.

Cited by 98 publications

References 42 publications

Management of Graves' Ophthalmopathy: Reality and Perspectives

Management of Graves' Ophthalmopathy: Reality and Perspectives

Igs from Patients with Graves’ Disease Induce the Expression of T Cell Chemoattractants in Their Fibroblasts

Cultured Human Fibroblasts Express Constitutive IL-16 mRNA: Cytokine Induction of Active IL-16 Protein Synthesis Through a Caspase-3-Dependent Mechanism

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