Steroid resistance in nasal polyposis: role of glucocorticoid receptor and TGF-beta1.

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-α and GR-β, is a potential mechanism underlying GC insensitivity. GCs modulate the expression of several cytokines, including transforming growth factor-β (TGF-β), 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-α binding capacity; Western blotting was used to evaluate GR-α, GR-β, and TGF-β expression and GR-α subcellular distribution. NPs were sampled in 32 patients during ethmoidectomy; NM was taken from 15 healthy patients during rhinoplasty. Results: GR-α was present in NPs and NM, with lower affinity for the ligand in NPs. GR-α was prevalent in the cytosol of NPs that were GR-α-negative to the binding assay. GR-β was expressed in NPs and absent in the majority of NM. TGF-β1 expression was higher in NPs than in NM.