Glucocorticoids Directly Affect Hyaluronan Production of Orbital Fibroblasts; A Potential Pleiotropic Effect in Graves’ Orbitopathy |
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Authors: | Erika Galgoczi Monika Katko Fruzsina Reka Papp Robert Csiki Sara Csiha Annamaria Erdei Miklos Bodor Bernadett Ujhelyi Zita Steiber Ferenc Gyory Endre V. Nagy |
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Affiliation: | 1.Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4032 Debrecen, Hungary;2.Doctoral School of Health Sciences, University of Debrecen, Nagyerdei Krt. 98, 4032 Debrecen, Hungary;3.Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4032 Debrecen, Hungary;4.Department of Surgery, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4032 Debrecen, Hungary |
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Abstract: | Orbital connective tissue expansion is a hallmark of Graves’ orbitopathy (GO). In moderate-to-severe active GO, glucocorticoids (GC) are the first line of treatment. Here we show that hydrocortisone (HC), prednisolone (P), methylprednisolone (MP), and dexamethasone (DEX) inhibit the hyaluronan (HA) production of orbital (OF) and dermal (DF) fibroblasts. HA production of GO OFs (n = 4), NON-GO OFs (n = 4) and DFs (n = 4) was measured by ELISA. mRNA expression of enzymes of HA metabolism and fibroblast proliferation was examined by RT-PCR and BrdU incorporation, respectively. After 24 h of GC treatment (1µM) HA production decreased by an average of 67.9 ± 3.11% (p < 0.0001) in all cell cultures. HAS2, HAS3 and HYAL1 expression in OFs also decreased (p = 0.009, p = 0.0005 and p = 0.015, respectively). Ten ng/mL PDGF-BB increased HA production and fibroblast proliferation in all cell lines (p < 0.0001); GC treatment remained effective and reduced HA production under PDGF-BB-stimulated conditions (p < 0.0001). MP and DEX reduced (p < 0.001, p = 0.002, respectively) PDGF-BB-induced HAS2 expression in OFs. MP and DEX treatment decreased PDGF-BB stimulated HAS3 expression (p = 0.035 and p = 0.029, respectively). None of the GCs tested reduced the PDGF-BB stimulated proliferation rate. Our results confirm that GCs directly reduce the HA production of OFs, which may contribute to the beneficial effect of GCs in GO. |
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Keywords: | Graves’ orbitopathy, hyaluronan, glucocorticoids, hyaluronan synthase, methylprednisolone, prednisolone, hydrocortisone, dexamethasone |
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