Overexpression of A20 Inhibits the Inflammatory Response During Dengue Fever Infection

Abstract

Aim: Dengue hemorrhagic fever is a devastating disease. This study aimed to investigate the role of A20 in dengue fever infection. Materials & methods: DENV2-infected human umbilical vein endothelial cells were transfected with shRNA-A20/CD14 and A20/CD14-mimics, respectively. The expressions of inflammatory and anti-inflammatory factors, A20 and downstream proteins of the NF-κB signaling pathway were detected. Results: A20 knockdown increased the expression of IL-6, IL-10, IL-8 and CD14 during dengue virus infection, whereas overexpression of A20 had the opposite effect. FACS revealed that A20 negatively regulated the expression of CD14. Conclusion: In DENV2-infected human umbilical vein endothelial cells overexpressing A20, TNF-α stimulation inhibited NF-κB-mediated inflammatory response by negative feedback. Furthermore, A20 could affect the release of inflammatory factors via negative regulation of CD14, thus affecting the entire inflammatory response.

Keywords: :

• A20
• CD14
• DENV2
• HUVEC
• IL-6
• IL-8
• IL-10
• inflammatory factors
• NF-κB
• TNF-α

Author’s contributions

XP Tang and WL Li conceived and designed the experiments. WL Li, MS Wu and PL Guo performed the experiments. FY Hu analyzed the data. LH Li contributed reagents/materials/analysis tools. WL Li wrote the paper.

Financial & competing interests disclosure

All authors sincerely acknowledge the support given by the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Second Provincial General Hospital, Number Eight People’s Hospital of Guangzhou, and thank the funding support from the Natural Science Foundation of Guangdong Province (no. 2013A020229002). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.