Adenovirus 7 Induces Interlukin-6 Expression in Human Airway Epithelial Cells via p38/NF-κB Signaling Pathway
- PMID: 33072092
- PMCID: PMC7538593
- DOI: 10.3389/fimmu.2020.551413
Adenovirus 7 Induces Interlukin-6 Expression in Human Airway Epithelial Cells via p38/NF-κB Signaling Pathway
Abstract
Human Adenovirus (AdV) infection is very common and usually has a significant impact on children. AdV-induced inflammation is believed to be one of the main causes of severe symptoms. However, an inflammatory response profile in the airway in AdV-infected children is still lacking, and the mechanism underlying AdV-induced inflammation in the airway is also poorly understood. In the current study, we determined the expression of a panel of inflammation cytokines in the airway samples from AdV 7 infected children and further investigated the molecular mechanism underlying AdV 7-induced cytokine expression. Our results showed that eight out of 13 tested inflammatory cytokines were significantly increased in nasal washes of AdV 7-infected children comparing to healthy control, with IL-6 showing the highest enhancement. AdV 7 infection of bronchial epithelial cell line and primary airway epithelial cells confirmed that AdV 7 increased IL-6 mRNA and protein expression in an infection dose-dependent manner. Promoter analysis revealed that AdV 7 infection transactivated IL-6 promoter and a NF-κB binding site in IL-6 promoter was involved in the transactivation. Further analysis showed that upon AdV 7 infection, NF-κB p65 was phosphorylated and translocated into nucleus and bound onto IL-6 promoter. Signaling pathway analysis revealed that p38/NF-κB pathway was involved in AdV 7 infection induced IL-6 elevation. Taken together, our study shows that AdV 7 infection triggers the expression of a range of inflammatory cytokines including IL-6 in the airway of infected children, and AdV 7 enhances IL-6 expression by transactivating IL-6 promoter via p38/NF-κB signaling pathway. Findings of our current study have provided more information toward a better understanding of AdV-induced airway inflammation, which might also benefit the development of intervention strategies.
Keywords: Adenovirus 7; Interlukin-6; airway epithelial cell; inflammation; p38/NF-κB signaling pathway.
Copyright © 2020 Qi, Wang, Wang and Deng.
Figures






Similar articles
-
[House dust mite extract activates EphA2-STAT3/p38 MAPK signaling pathway in airway epithelial cells to mediate airway inflammation].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2021 Jan;37(1):31-38. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2021. PMID: 33441226 Chinese.
-
Human adenovirus type 19 infection of corneal cells induces p38 MAPK-dependent interleukin-8 expression.Virol J. 2008 Jan 25;5:17. doi: 10.1186/1743-422X-5-17. Virol J. 2008. PMID: 18221537 Free PMC article.
-
Viral induction of inflammatory cytokines in human epithelial cells follows a p38 mitogen-activated protein kinase-dependent but NF-kappa B-independent pathway.J Immunol. 2003 Oct 1;171(7):3768-74. doi: 10.4049/jimmunol.171.7.3768. J Immunol. 2003. PMID: 14500677
-
IL-36 family cytokines in protective versus destructive inflammation.Cell Signal. 2020 Nov;75:109773. doi: 10.1016/j.cellsig.2020.109773. Epub 2020 Sep 6. Cell Signal. 2020. PMID: 32898612 Review.
-
IL32: The multifaceted and unconventional cytokine.Hum Immunol. 2021 Sep;82(9):659-667. doi: 10.1016/j.humimm.2021.05.002. Epub 2021 May 21. Hum Immunol. 2021. PMID: 34024634 Review.
Cited by
-
In Vitro Antiviral and Anti-Inflammatory Activities of N-Acetylglucosamine: Development of an Alternative and Safe Approach to Fight Viral Respiratory Infections.Int J Mol Sci. 2023 Mar 7;24(6):5129. doi: 10.3390/ijms24065129. Int J Mol Sci. 2023. PMID: 36982205 Free PMC article.
-
Comparisons of lymphocytes profiles and inflammatory cytokines levels in blood of patients with differed severity of infection by human adenovirus type 7.BMC Infect Dis. 2023 Mar 22;23(1):174. doi: 10.1186/s12879-023-08132-z. BMC Infect Dis. 2023. PMID: 36949406 Free PMC article.
-
Cytokine Responses to Adenovirus and Adenovirus Vectors.Viruses. 2022 Apr 24;14(5):888. doi: 10.3390/v14050888. Viruses. 2022. PMID: 35632630 Free PMC article. Review.
-
Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression.Front Immunol. 2021 Jun 7;12:691879. doi: 10.3389/fimmu.2021.691879. eCollection 2021. Front Immunol. 2021. PMID: 34163488 Free PMC article.
-
Roles of Interleukin-6-mediated immunometabolic reprogramming in COVID-19 and other viral infection-associated diseases.Int Immunopharmacol. 2022 Sep;110:109005. doi: 10.1016/j.intimp.2022.109005. Epub 2022 Jun 28. Int Immunopharmacol. 2022. PMID: 35780641 Free PMC article. Review.
References
-
- Chuang Y, Chiu C-H, Wong K-S, Huang J-G, Huang YC, Chang LY, et al. . Severe adenovirus infection in children. J Microbiol Immunol Infect. (2003) 36:37–40. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources