Mucin 1 downregulation impairs the anti-necroptotic effects of glucocorticoids in human bronchial epithelial cells

Publication date: Available online 7 February 2019Source: Life SciencesAuthor(s): Huojun Zhang, Qian Liu, Luxia Kong, Shuyun XuAbstractAimsTo investigate whether mucin 1 (MUC1) downregulation reduced the sensitivity of tumor necrosis factor-alpha (TNF-α)-induced bronchial epithelial cells to glucocorticoid-mediated necroptosis and explore the underlying mechanisms.Main methodsThe human lung bronchial epithelial cell line (16HBE) was transfected with small interfering RNA (siRNA) against MUC1 and then stimulated by TNF-α, where some cells were pretreated with dexamethasone. Flow cytometry was performed to analyze necroptosis in 16HBE cells, and western blot analysis was used to detect protein expression levels of MUC1, glucocorticoid receptor (GR)α, GRβ, NF-κB p65, phospho-p65 (p-p65), and histone deacetylase-2 (HDAC2). Additionally, nuclear translocation of MUC1 and GRα was assessed by immunofluorescence.Key findingsWe observed that MUC1 downregulation by siRNA significantly augmented TNF-α-induced necroptosis in 16HBE cells, and that dexamethasone showed impaired anti-necroptotic effects of MUC1 downregulation. Furthermore, we found that GRα nuclear translocation was inhibited in 16HBE cells with MUC1 downregulation, and that dexamethasone-mediated inhibition of p65 phosphorylation was lower in cells transfected with MUC1-siRNA compared to those transfected with negative control siRNA.SignificanceImpaired GRα nuclear translocation and inhibited p-p65 expression migh...

Source: Life Sciences - February 7, 2019 Category: Biology Source Type: research