Objectives: Glucocorticoids (GCs) are the first line therapy in moderate to severe, active thyroid eye disease (TED). While their beneficial immunosuppressive effects are well known, direct connective tissue effects are less characterized. The accumulation of extracellular matrix component hyaluronan (HA) and increased proliferation rate of fibroblasts are hallmarks connective tissue changes in TED. We examined the effect of methylprednisolone (MP), prednisolone (P), hydrocortisone (HC) and dexamethasone (DEX) on HA synthesis and proliferation of orbital (OF) and dermal fibroblasts (DF) in culture.
Methods: In the presence or absence of MP, P, HC or DEX, mRNA expression of hyaluronan synthases (HAS1, HAS2, and HAS3) and HA production were measured by RT-PCR and ELISA respectively. TED orbital (n = 4), non-TED orbital (n = 4) and dermal fibroblastslines (n = 4) were used. The effect of GCs on proliferation was measured using a BrdU incorporation assay.
Results: After 24-hour GC treatment (1 µM), HA production of TED and non-TED OFs, as well as DFs decreased by 61.1 %, 62.9 % and 77.8 % for DEX, 57.5 %, 63.8 %, 72.6 % for MP, 53.8 %, 58.7 %, 72.2 % for P, and 50.7 %, 52.7% and 72.3 % for HC, respectively (P < 0.0001 for all GCs tested). GCs reduced HAS3 expression (P < 0.0001) in all cell cultures irrespective of the site of origin, while only DEX could decrease HAS2 expression in all fibroblast cultures tested (TED OFs P = 0.0239, non-TED P = 0.0044 DFs P < 0.0001). The proliferation rate was not influenced by GCs, except a 27 % and 18 % reduction in non-GO OFs and DFs after DEX treatment (P = 0.0165 and P = 0.0227, respectively).
Conclusions: We confirmed that glucocorticoids act directly on HAS mRNA expression and HA production of human OFs. We assume that the reduction in HAS gene expression and inhibition of HA production contribute to the beneficial effect of glucocorticoids in TED.
10 Sep 2022 - 13 Sep 2022