Mucin 1 downregulation associates with corticoid resistance in chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyps

Background: Corticoid resistance is relevant because implies a lower anti-inflammatory activity of corticoids. Diseases such as Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) may have corticoid resistance, while Chronic Obstructive Pulmonary Disease (COPD) is itself. Mucin 1 (MUC1) shows anti-inflammatory properties, and its cytoplasmic tail (CT) modulates transcription factors. Anti-inflammatory effect of corticoids requires glucocorticoid receptor (GR) nuclear translocation, then we hypothesize that MUC1 could modulate this mechanism Objective: To determine the role of MUC1 in corticoid effectiveness in CRSwNP and COPD Methods: The expression of MUC1 and MUC1-CT was determined in CRSwNP polyps and healthy or COPD lung parenchyma using RT-PCR, Western blotting and Immunohistochemistry. Lack of MUC1 with RNA interference (siRNA-MUC1) in BEAS -2B cell line was used to estimate its importance in the anti-inflammatory activity of dexamethasone Results: MUC1 expression was reduced in nasal polyps that were resistant to oral corticoids (NP-CR) and in lung parenchyma from smokers and COPD patients. NP-CR derived primary epithelial cells showed lack of the anti-inflammatory effects of dexamethasone. In siRNA-MUC1 Beas-2B, dexamethasone had weaker anti-inflammatory effects. Immunoprecipitation revealed that MUC1-CT and GRα interact and translocate to the nucleus in response to dexamethasone. MUC1-CT-GRα complex was reduced in NP-CR tissue Conclusion: Corticoid response that mediates GRα nuclear translocation requires MUC1-CT. The low expression of MUC1 in patients with CRSwNP or COPD may participate in corticoid resistance.