Abstract
Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, we found that interleukin-8 (IL-8) was upregulated by PDCoV infection. We then demonstrated that PDCoV E protein induced IL-8 production and that the TM domain and the C-terminal domain of the E protein were important for IL-8 production. Subsequently, we showed here that deleting the AP-1 and NF-κB binding motif in porcine IL-8 promoter abrogated its activation, suggesting that IL-8 expression was dependent on AP-1 and NF-κB. Furthermore, PDCoV E induced IL-8 production, which was also dependent on the NF-κB pathway through activating nuclear factor p65 phosphorylation and NF-κB inhibitor alpha (IκBα) protein phosphorylation, as well as inducing the nuclear translocation of p65, eventually resulting in the promotion of IL-8 production. PDCoV E also activated c-fos and c-jun, both of which are members of the AP-1 family. These findings provide new insights into the molecular mechanisms of PDCoV-induced IL-8 production and help us further understand the pathogenesis of PDCoV infection.
Keywords: E; IL-8; Inflammation; PDCoV.
【저자키워드】 Inflammation, IL-8, E, PDCoV., 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, coronavirus, Pathogenesis, IL-6, Infection, interleukin-6, Local, molecular mechanism, chemokine, Cytokine release syndrome, E protein, Phosphorylation, Alpha, inhibitor, antiviral immunity, expression, binding, NF-κB, NF-κB pathway, C-terminal domain, Proinflammatory cytokine, acute respiratory syndrome, Activation, domain, nuclear translocation, help, life-threatening, Severe case, AP-1, motif, promoter, IκBα, protein phosphorylation, nuclear, resulting, caused, facilitate, activated, dependent on, demonstrated, induce, upregulated, deleting, abrogated, activating, p65, 【제목키워드】 E protein, NF-κB, Activation, AP-1, induce,