Apremilast mitigates interleukin (IL)-13-induced inflammatory response and mucin production in human nasal epithelial cells (hNECs)

ABSTRACT

Interleukin (IL)-13-associated inflammatory response is important for the pathogenesis of allergic rhinitis (AR). Apremilast is a phosphodiesterase-4 (PDE4) inhibitor approved for psoriasis treatment. Here, we investigated the potential effects of Apremilast against IL-13-induced injury in human nasal epithelial cells (hNECs). Firstly, Apremilast ameliorated oxidative stress in IL-13-challenged cells by decreasing the levels of reactive oxygen species (ROS) and the production of malondialdehyde (MDA). Secondly, Apremilast inhibited the expressions of IL-6 and IL-8. Moreover, Apremilast inhibited the expressions of the chemokines colony-stimulating factor 2 (CSF2) and chemokine ligand 11 (CCL11). Interestingly, exposure to IL-13 increased the expressions of mucin 4 and mucin 5AC (MUC5AC), which was ameliorated by treatment with Apremilast. Interestingly, we found that Apremilast inhibited the phosphorylation of c-Jun-N-terminal kinase (JNK). Importantly, Apremilast reduced the levels of c-fos and c-Jun, the two AP-1 subfamilies. The luciferase reporter assay demonstrates that Apremilast reduced the transcriptional activity of activator protein 1 (AP-1). Lastly, we found that Apremilast prevented the activation of nuclear factor kappa-B (NF-κB) by decreasing the levels of nuclear NF-κB p65 and the luciferase activity of the NF-κB reporter. In summary, we conclude that Apremilast possesses a protective effect against IL-13-induced inflammatory response and mucin production in hNECs by inhibiting the activity of AP-1 and NF-κB.

KEYWORDS:

• Apremilast
• IL-13
• allergic rhinitis
• mucin
• NF-κB

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Jia Liang and Bin Zou contributed to experimental design and data analysis; Jia Liang, RuoXiao Zhuang, XueYao Sun, and Feng Zhang contributed to the investigation; Bin Zou prepared the manuscript. All authors have read and approved the manuscript.

Ethics approval and consent to participate

The protocol of this study was approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University.

Consent for publication

All the authors have read and approved the final submission of this study.

Availability of data and materials

Data and materials of this study are available upon reasonable request to the corresponding authors.

Additional information

Funding

This study was funded by the ‘Joint project of Chongqing Science and Technology Commission and Health Commission [2020MSXM040]’.