Transcription factor AP‑2α negatively regulates thymic stromal lymphopoietin expression in respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection enhances the cell-mediated immune responses of type 2 helper T cells and promotes the progression of allergic inflammation and asthma by producing thymic stromal lymphopoietin (TSLP), especially long isoform TSLP (lfTSLP). However, the role of short isoform TSLP (sfTSLP) in RSV infection remains to be elucidated. The present study was designed to demonstrate the role of both lfTSLP and sfTSLP, as transcription regulators, in RSV infection. The expression of lfTSLP and sfTSLP in RSV-infected Beas-2B cells was analyzed. Activating protein 2 (AP-2)alpha was overexpressed or knocked down to detect the changes in sfTSLP and lfTSLP expression. Luciferase reporter plasmid and chromatin immunoprecipitation experiments demonstrated that AP-2 alpha bound to the sfTSLP promoter region. LfTSLP and sfTSLP increased while AP-2 alpha decreased in RSV-infected Beas-2B cells. In the Beas-2B cells, AP-2 alpha was found to negatively regulate the activity of the sfTSLP promoter and the mRNA level of sfTSLP. AP-2 alpha also negatively regulated the expression of lfTSLP at both the mRNA and protein levels. The results of the chromatin immunoprecipitation assay indicated that AP-2 alpha bound to the core promoter region of sfTSLP. These results confirmed that the transcription factor AP-2 alpha can repress the expression of lfTSLP and sfTSLP in bronchial epithelial cells in RSV infection.