Archives of Virology

, Volume 163, Issue 5, pp 1209–1217 | Cite as

Respiratory syncytial virus infection up-regulates TLR7 expression by inducing oxidative stress via the Nrf2/ARE pathway in A549 cells

  • Tao Sun
  • Hai-yang Yu
  • Chuan-long Zhang
  • Tong-na Zhu
  • Sheng-hai Huang
Original Article

Abstract

In order to better understand the early pathways of the pathogenesis of, and immune response to, RSV, herein, we explored the relationship between TLR7 expression and oxidative stress induction following RSV infection in A549 cells. We studied the intervening effects of the Nrf2/ARE pathway agonist butylated hydroxyanisole (BHA) and inhibitor trigonelline (TRI) on TLR7 modulation or oxidative stress induction. For comparison purposes, we set up seven treatment groups in this study, including RSV-treated cells, BHA + RSV-treated cells, TRI + RSV-treated cells, normal cell controls, inactivated RSV controls, BHA controls and TRI controls. We measured changes in TLR7, IL-6, TNF-α mRNA using RT-PCR and IL-6, TNF-α and IL-1β protein using ELISA as well as TLR7, Nrf2 and HO-1 protein using Western blot in A549 cells from the different treatment groups. We also assessed changes in cell proliferation and measured changes in ·OH and NO in A549 cells from the different treatment groups. The results indicate that TLR7 up-regulation is related to RSV infection and the induction of oxidative stress and that TLR7 expression was mediated by the anti-inflammatory effects of Nrf2/ARE pathway inhibitors or agonists. Our experiments may help elucidate the underlying pathology of RSV infection and suggest potential therapeutic targets for drug development and the prevention of RSV-induced human diseases.

Abbreviations

RSV

Respiratory syncytial virus

TLR7

Toll-like receptor 7

pi

Post infection

BHA

Butylated hydroxyanisole

TRI

Trigonelline

Nrf2

NF-E2-related factor 2

TLRs

Toll-like receptors

OH

Hydroxyl radicals

ssRNA

Single-stranded RNA

COPD

Chronic obstructive pulmonary disease

AOE

Antioxidant enzyme

ROS

Reactive oxygen species

HO-1

Heme oxygenase-1

HEp-2

Human laryngeal carcinoma epithelial cells

Notes

Acknowledgements

We thank Ms. Xiao-yan Zhang for her technical assistance and LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

705_2018_3739_MOESM1_ESM.doc (41 kb)
Supplementary material 1 (DOC 41 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Tao Sun
    • 1
  • Hai-yang Yu
    • 1
  • Chuan-long Zhang
    • 3
  • Tong-na Zhu
    • 1
  • Sheng-hai Huang
    • 1
    • 2
  1. 1.Department of Microbiology, School of Basic Medical ScienceAnhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.School of Life SciencesAnhui Medical UniversityHefeiPeople’s Republic of China
  3. 3.Department of PediatricsThe People’s Hospital of Lu’an CityLu’anPeople’s Republic of China

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