ABSTRACT
Title
Evaluation of biochemical features in nasal polyposis
Authors
V. Carriero1, S. Racca1, G. Abbadessa1, C. Ondolo2, S. Aversa2, S. Conticello2, F. Di Carlo1
1Dept of Clinical and Biological Sciences, School of Medicine, University of Torino
2Dept of Otolaryngology, “San Luigi Gonzaga” Hospital, University of Torino Orbassano, Torino
1Dept of Clinical and Biological Sciences, School of Medicine, University of Torino
2Dept of Otolaryngology, “San Luigi Gonzaga” Hospital, University of Torino Orbassano, Torino
Abstract
Nasal polyps (NPs) are benign lesions arising from the nasal mucosa, characterized by inflammatory infiltrates. Topical and systemic glucocorticoids (GC) are currently considered the drugs of choice for the treatment of NP, leading to success in 60-80%. Cell resistance to GC may be implicated in clinical failure in the treatment of NPs. A mechanism supposed to cause the GC-resistance involves both isoforms of GC receptor, GR-α and GR-β In fact either the increase of GR-β, the decrease of GR-α or the imbalance in the GR-α/GR-β ratio have been cited as implicated in cell resistance. Moreover GC modulate the expression of several cytokines, such as TGF-β1, a growth factor which may contribute to cellular proliferation in NPs.
The aim of this study was to investigate some biomolecular features of GR-resistant NPs and possible differences from normal tissues.
We evaluated both in NPs and normal mucosa GR-α, GR-β and TGF-β expression by Western blotting (WB) and GR- α binding capacity by “binding assay”. Moreover, to check GR-α activation we verified the receptors subcellular distribution. We also studied the expression of GR- α, GR-β and TGF-β1 in NP samples spread in a growth medium and treated with prednisone for 24 and 48 hours.Biopsies of NP were obtained from 30 patients refractory to steroid treatment who needed operative removal of polyps, while control mucosal specimens were obtained from 15 donors NP-free.
GRs-α were present both in NPs and normal mucosa but showed lower affinity for the ligand in NPs. GRs-α were prevalent in the cytosol of most of the NPs which resulted GR-negative to “binding assay”. GRs-β were expressed in NPs but were absent in the majority of controls. TGF-β1 expression was higher in NPs than normal mucosa. In NP cultures prednisone decreased the cytokine level and the GR-α and GR-β expression in the majority of cases.
The results obtained so far suggest that both GRs-β and TGF-β1 are involved in the pathogenesis of NPs. Further investigation needs to be conducted to elucidate their exact role.
The aim of this study was to investigate some biomolecular features of GR-resistant NPs and possible differences from normal tissues.
We evaluated both in NPs and normal mucosa GR-α, GR-β and TGF-β expression by Western blotting (WB) and GR- α binding capacity by “binding assay”. Moreover, to check GR-α activation we verified the receptors subcellular distribution. We also studied the expression of GR- α, GR-β and TGF-β1 in NP samples spread in a growth medium and treated with prednisone for 24 and 48 hours.Biopsies of NP were obtained from 30 patients refractory to steroid treatment who needed operative removal of polyps, while control mucosal specimens were obtained from 15 donors NP-free.
GRs-α were present both in NPs and normal mucosa but showed lower affinity for the ligand in NPs. GRs-α were prevalent in the cytosol of most of the NPs which resulted GR-negative to “binding assay”. GRs-β were expressed in NPs but were absent in the majority of controls. TGF-β1 expression was higher in NPs than normal mucosa. In NP cultures prednisone decreased the cytokine level and the GR-α and GR-β expression in the majority of cases.
The results obtained so far suggest that both GRs-β and TGF-β1 are involved in the pathogenesis of NPs. Further investigation needs to be conducted to elucidate their exact role.