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

He,Jia; Cao,Qian; Feng,Dan‑Dan; Chen,Jia‑He; Zhou,Guo‑Ping

doi:10.3892/mmr.2020.11192

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

Authors:
- Jia He
- Qian Cao
- Dan‑Dan Feng
- Jia‑He Chen
- Guo‑Ping Zhou
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Affiliations: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: May 28, 2020 https://doi.org/10.3892/mmr.2020.11192
Pages: 1639-1646

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Abstract

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)α was overexpressed or knocked down to detect the changes in sfTSLP and lfTSLP expression. Luciferase reporter plasmid and chromatin immunoprecipitation experiments demonstrated that AP‑2α bound to the sfTSLP promoter region. LfTSLP and sfTSLP increased while AP‑2α decreased in RSV‑infected Beas‑2B cells. In the Beas‑2B cells, AP‑2α was found to negatively regulate the activity of the sfTSLP promoter and the mRNA level of sfTSLP. AP‑2α also negatively regulated the expression of lfTSLP at both the mRNA and protein levels. The results of the chromatin immunoprecipitation assay indicated that AP‑2α bound to the core promoter region of sfTSLP. These results confirmed that the transcription factor AP‑2α can repress the expression of lfTSLP and sfTSLP in bronchial epithelial cells in RSV infection.

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