Stimulation of glucose utilization and glycosaminoglycans production by fibroblasts derived from retrobulbar tissue

Sisson, James C.

doi:10.1016/0014-4835(71)90151-5

Cited by 20 publications

(9 citation statements)

References 22 publications

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“…Coupled with our recent report that sera from a majority of patients with Graves' disease immunoreact with a 23-kDa protein in fibroblasts from all anatomical sites tested (19), we conclude that regional differences relate to some but not all phenotypic characteristics of that cell type. In early studies, Sisson and colleagues characterized GAG production in fibroblasts derived from retroocular connective tissue (20) and demonstrated that lymphocytes could stimulate both hyaluronate accumulation and glucose utilization (21). Those workers were able to show that glucocorticoids added to the culture medium could block that lymphocyte stimulation (22).…”

Section: Discussionmentioning

confidence: 98%

Hormonal Regulation of Hyaluronate Synthesis in Cultured Human Fibroblasts: Evidence for Differences between Retroocular and Dermal Fibroblasts

Smith

Bahn

Gorman

1989

The Journal of Clinical Endocrinology & Metabolism

106

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Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts.

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Section: Discussionmentioning

confidence: 98%

Hormonal Regulation of Hyaluronate Synthesis in Cultured Human Fibroblasts: Evidence for Differences between Retroocular and Dermal Fibroblasts

Smith

Bahn

Gorman

1989

The Journal of Clinical Endocrinology & Metabolism

106

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“…Other studies focused on fibroblasts, the source of glycosaminoglycans (GAG) that accumulate in the orbit and skin in GO and dermopathy. Thus, lymphocytes (8) and a variety of cytokines enhance GAG production by retro-orbital fibroblasts (reviewed in refs. 9,10).…”

Section: Introductionmentioning

confidence: 99%

Elephantiasic Pretibial Myxedema: Insight into and a Hypothesis Regarding the Pathogenesis of the Extrathyroidal Manifestations of Graves' Disease

Rapoport

Alsabeh

Aftergood

et al. 2000

Thyroid

110

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The basis for the extrathyroidal manifestations of Graves' ophthalmopathy (GO) and dermopathy are not well understood. We describe immunohistochemical studies on the skin of a patient with an extreme, elephantiasic form of Graves' dermopathy that developed after periods of prolonged standing with dependent edema. Excision of part of the lesion with subsequent skin grafting from a normal donor site resulted in recurrence of the disease at the original site as well as in development of disease at the donor site. A murine monoclonal antibody reacted with the thyrotropin receptor (TSHR) or a cross-reacting protein in fibroblast-like cells in the patient's upper dermis and, surprisingly, with dermal cells from unaffected individuals. The patient's dermis containing lymphoid follicles comprising B cells and CD3+, CD4+ T cells, with few CD8+ T cells. CD21+ cells (most likely follicular dendritic cells) were also present in the dermis. Based on past and present observations, we raise an unifying hypothesis to explain the diverse extrathyroidal manifestations of Graves' disease and their apparent lack of association with TSHR autoantibodies. As opposed to the present concept that these phenomena relate to site-specific properties on preadipocytes or fibroblasts, we suggest that clinically evidence GO and dermopathy are primarily caused by local factors (particularly in the orbit) superimposed on a systemic, low-grade connective tissue inflammation.

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“…For skin fibroblasts, this synthesis is modulated by thyroid hormones (1). Additionally, it has been shown that lymphocytes can stimulate glycosaminoglycan production by retrobulbar fibroblasts (2)(3)(4). Glycosaminoglycans accumulate in retroocular tissues of patients with GO (5).…”

mentioning

confidence: 99%

Human Retroocular Fibroblastsin Vitro: A Model for the Study of Graves' Ophthalmopathy

Bahn

Gorman

Woloschak

et al. 1987

The Journal of Clinical Endocrinology & Metabolism

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Orbital connective tissue and extraocular muscles are histologically abnormal in patients with Graves' ophthalmopathy (GO). Although extraocular muscles have been extensively studied as a target for autoimmune attack in the disease, no system has been available to study retroocular fibroblasts in GO. We developed a technique to isolate fibroblasts from minced explants of connective tissue removed in the course of transantral orbital decompression surgery for GO. Postmortem specimens from individuals without evidence of thyroid disease were obtained from the same anatomical site. Confluent cells could be passaged at least 10 times with stable morphology and frozen with greater than 75% viability. An enzyme-linked immunosorbent assay was used to study the in vitro binding of serum immunoglobulin G (IgG) to these cells. We found no difference in the degree of specific binding between GO cells and cells from normal individuals. However, there was significantly greater binding of IgG from GO sera than of that from normal serum to retroocular GO fibroblasts. These results suggest that serum IgG autoantibodies against normal retroocular fibroblasts are present in some GO patients.

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Stimulation of glucose utilization and glycosaminoglycans production by fibroblasts derived from retrobulbar tissue

Cited by 20 publications

References 22 publications

Hormonal Regulation of Hyaluronate Synthesis in Cultured Human Fibroblasts: Evidence for Differences between Retroocular and Dermal Fibroblasts

Hormonal Regulation of Hyaluronate Synthesis in Cultured Human Fibroblasts: Evidence for Differences between Retroocular and Dermal Fibroblasts

Elephantiasic Pretibial Myxedema: Insight into and a Hypothesis Regarding the Pathogenesis of the Extrathyroidal Manifestations of Graves' Disease

Human Retroocular Fibroblastsin Vitro: A Model for the Study of Graves' Ophthalmopathy

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