Tuberc Respir Dis > Volume 48(5); 2000 > Article
Tuberculosis and Respiratory Diseases 2000;48(5):682-698.
DOI:    Published online May 1, 2000.
Inhibitory mechanism on NF-kB transactivation by dexamethasone in pulmonary epithelial cells.
Kye Young Lee, Yoon Seop Kim, Mi Hye Ko, Jae Seok Park, Young Koo Jee, Keun Youl Kim, Sahng June Kwak
Glucocorticoid receptor (GR) functions as a suppressor of inflammation by inhibiting the expression of many cytokine gene activated by NF-κB. The goal of this study is to investigate the mechanism by which GR repress NF-κB activation in lung epithelial cells. We used A549 and BEAS-2B lung epithelial cell lines. Using IgGκ-NF-κB luciferase reporter gene construct, we found that dexamethasone significantly suppressed TNF-α-induced NF-κB activation and the overexpression of GR showed dose-dependent reduction of TNF-α-induced NF-κB activity in both cell lines. However, DNA binding of NF-κB induced by TNF-α in electromobility shift assay was not inhibited by dexamethasone. Super shift assay with anti-p65 antibody demonstrated the existence of p65 in NF-κB complex induced by TNF-α Western blot showed that IκBα degradation induced by TNF-α was not affected by dexamethasone and IκBκ was not induced by dexamethasone, neither. To evaluate p65 specific transactivation, we adopted co-transfection study of Ga14-p65TA1 or TA2 fusion protein expression system together with 5xGa14-luciferase vector. Co-transfection of GR with Ga14-p65TA1 or TA2 repressed luciferase activity profoundly to the level of 10-20% of p65TA1- or TA2-induced transcriptional activity. And this transrepressional effect was abolished by co-transfection of CBP or SRC-1 expression vectors. These results suggest that Gr-mediated transrepression of NF-κB in lung epithelial cells is through competing for binding to limiting amount of transcriptional coactivators, CBP or SRC-1.
Key Words: NF-kappa B, Glucocorticoid receptor, Transactivation, p65

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