Graves' disease (GD) and Hashimoto's
thyroiditis (HT) are autoimmune processes often associated with
hyperthyroidism and
hypothyroidism, respectively. Despite their diverging clinical presentations, immune activation drives both diseases and results in connective tissue accumulation of the nonsulfated
glycosaminoglycan,
hyaluronan. The hydrophilic property of
hyaluronan contributes to the pathogenesis of
thyroid-associated ophthalmopathy, dermopathy and hypothyroid
myxedema. Whether
hyaluronan accumulates in the thyroid and plays a role in
goiter formation in GD and HT remains unknown. We report here that levels of
hyaluronan are increased in thyroid tissue from individuals with both diseases compared with glands uninvolved with autoimmune disorders. The transcript encoding
hyaluronan synthase (HAS)-3, one of three mammalian HAS
isoforms, was detected in thyroid tissue. Isolated thyrocytes in primary culture express all three HAS
isoforms when treated with IL-1beta. Thyrocytes and thyroid fibroblasts produce
hyaluronan under basal culture conditions and IL-1beta enhances levels of this molecule in both cell types. On a per-cell basis, fibroblasts produce more
hyaluronan than do thyrocytes under basal conditions and after
cytokine treatment. Synthesis in thyrocytes can also be altered by increasing serum concentration in the medium and by modifying culture density. Our findings suggest that
hyaluronan accumulation in thyroid tissue might derive from thyrocytes and fibroblasts. Moreover, this
glycosaminoglycan becomes more abundant as a consequence of
autoimmune disease. It may therefore contribute to increased thyroid volume in GD and HT. Coupled with the newly identified influence exerted by
hyaluronan on immunocompetent cells, our findings represent potentially important insights into the pathogenesis of autoimmune
thyroid diseases.