Steroid resistance in nasal polyposis: role of glucocorticoid receptor and TGF-β1

Background: Glucocorticoids (GCs) are considered drugs of choice for treating nasal polyps (NPs). However, a subset of patients shows a limited clinical response even to high doses of GCs. Altered expression of glucocorticoid receptors (GRs), namely GR-alpha and GR-beta, is a potential mechanism underlying GC insensitivity. GCs modulate the expression of several cytokines, including transforming growth factor-beta (TGF-beta), which may contribute to cellular proliferation in NPs. The study investigates some biomolecular features of GC-resistant NPs, and examines possible differences from normal mucosa (NM). Methodology: Radioligand binding assay (binding) was used to determine GR-alpha binding capacity; Western blotting was used to evaluate GR-alpha, GR-beta, and TGF-beta expression and GR-alpha subcellular distribution. NPs were sampled in 32 patients during ethmoidectomy; NM was taken from 15 healthy patients during rhinoplasty. Results: GR-alpha was present in NPs and NM, with lower affinity for the ligand in NPs. GR-alpha was prevalent in the cytosol of NPs that were GR-alpha-negative to the binding assay. GR-beta was expressed in NPs and absent in the majority of NM.TGF-beta 1 expression was higher in NPs than in NM. Conclusions: GR-beta and TGF-beta 1 might be involved in NP pathogenesis, but their role in modulating GC sensitivity is still unclear.