Effect of Tumor Necrosis Factor-α, Interferon-γ, and Transforming Growth Factor-β on Adipogenesis and Expression of Thyrotropin Receptor in Human Orbital Preadipocyte Fibroblasts1
Graves’ ophthalmopathy (GO) is an orbital autoimmune disease that is closely associated with Graves’ hyperthyroidism. Examination of retroorbital tissues in GO reveals an accumulation of glycosaminoglycans, increased fat volume, lymphocytic infiltration, and the presence of several inflammatory cyto...
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Published in | The journal of clinical endocrinology and metabolism Vol. 86; no. 2; pp. 903 - 908 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.02.2001
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Online Access | Get full text |
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Summary: | Graves’ ophthalmopathy (GO) is an orbital autoimmune disease that is
closely associated with Graves’ hyperthyroidism. Examination of
retroorbital tissues in GO reveals an accumulation of
glycosaminoglycans, increased fat volume, lymphocytic infiltration, and
the presence of several inflammatory cytokines. A subpopulation of
human orbital fibroblasts can be differentiated in vitro
into cells with the morphologic features of adipocytes. We demonstrated
recently that these differentiated cultures show increased expression
of functional TSH receptor (TSHr). To determine whether the presence of
inflammatory cytokines might impact adipogenesis or TSHr expression in
these cultures, we treated orbital fibroblasts from normal individuals
or GO patients with tumor necrosis factor-α (TNF-α), interferon-γ
(IFN-γ), or transforming growth factor-β. We found that each
of these cytokines inhibits TSH-dependent cAMP production and TSHr gene
expression, and that TNF-α and IFN-γ also inhibit morphological
adipocyte differentiation. When cytokines were added after
differentiation, the inhibition was less pronounced. Our results
suggest that TNF-α, IFN-γ, and transforming growth factor-β may
act within the orbit in GO to modulate expression of the putative
orbital autoantigen, TSHr. In addition, the former two cytokines may
play a role in determining the extent to which the volume of the
orbital adipose tissue increases in this condition. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.86.2.7188 |