6533b831fe1ef96bd1298d2a

RESEARCH PRODUCT

LATE-BREAKING ABSTRACT: MUC1 downregulation induces corticosteroid resistance in asthma'sin vitroandin vivomodels

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Background: Corticosteroids are in the first-line of Asthma treatment. However a subset of asthmatic patients is insensitive to anti-inflammatory effects of corticosteroids. Our previous data demonstrated that MUC1 downregulation correlates corticosteroid resistance in Nasal Polyposis and COPD. We hypothesized that MUC1 is also involved in corticosteroid resistance in Asthma. Objective: To analyze the role of MUC1 in the corticosteroid effectiveness in Asthma9s in vitro and in vivo models. Methods: 20 patients with steroid resistant Asthma were recruited. The expression of MUC1 was determined by real-time PCR in inflammatory cells from peripheral blood. HMVEC-L and U937 cells knockdown with RNA interference for MUC1 (siRNA-MUC1) was used to analyze effects of Dexamethasone (Dexa) by Flow Chamber and Migration assays, respectively. MUC1-KO mouse model of acute Asthma was treated with Dexa and pulmonary inflammation was evaluated byPositron emission tomography (PET-CT). Different inflammatory components were analyzed in mouse lungs and bronchoalveolar lavage by ELISA, histology, RT-PCR, immunofluorescence and Western Blot. Cells from WT and MUC1-KO mice were isolated to perform Flow Chamber and Migration assays to compare Dexa effects. Results: MUC1 expression was downregulated in inflammatory cells from patients with steroid resistant Asthma. MUC1 knockdown in HMVEC-L and U937 cells induced a lack of sensitive to the anti-inflammatory effects of Dexa in cell migration and endothelial adhesion. PET-CT and following analysis of Asthmatic MUC1-KO mice showed a less effect of Dexa compared to WT. Conclusion: MUC1 downregulation may lack the anti-inflammatory effects of corticosteroids in Asthma.