Oxidative stress modulates the expression of toll‑like receptor 3 during respiratory syncytial virus infection in human lung epithelial A549 cells

Wang,Min‑Min; Lu,Min; Zhang,Chuan‑Long; Wu,Xuan; Chen,Jing‑Xian; Lv,Wei‑Wei; Sun,Tao; Qiu,Huan; Huang,Sheng‑Hai

doi:10.3892/mmr.2018.9089

Oxidative stress modulates the expression of toll‑like receptor 3 during respiratory syncytial virus infection in human lung epithelial A549 cells

Authors:
- Min‑Min Wang
- Min Lu
- Chuan‑Long Zhang
- Xuan Wu
- Jing‑Xian Chen
- Wei‑Wei Lv
- Tao Sun
- Huan Qiu
- Sheng‑Hai Huang
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Affiliations: Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Pediatrics, The People's Hospital of Lu'an City, Lu'an, Anhui 237005, P.R. China
Published online on: May 29, 2018 https://doi.org/10.3892/mmr.2018.9089
Pages: 1867-1877

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Abstract

Toll‑like receptor 3 (TLR3) can react with double stranded RNA and is involved in the inflammatory response to respiratory syncytial virus (RSV) infection. Also, oxidative stress has been reported to be involved in RSV infection. However, the correlation between oxidative stress and TLR3 activation during RSV infection is unclear. Therefore, the present study investigated the association between TLR3 expression and oxidative stress modulation during RSV infection in A549 cells. For comparison, seven treatment groups were established, including RSV‑treated cells, N‑acetyl‑L‑cysteine (NAC)+RSV‑treated cells, oxidant hydrogen peroxide (H2O2)+RSV‑treated cells, normal cell control, inactivated RSV control, NAC control and H2O2 control. The mRNA expression changes of TLR3, interferon regulatory factor‑3 (IRF3), nuclear factor‑κB (NF‑κB) and superoxide dismutase 1 (SOD1) were measured using semi‑quantitative reverse transcription‑polymerase chain reaction, and the protein changes of TLR3 and phospho‑NF‑κB p65 were determined using western blot in A549 cells from the different treatment groups. The present study also evaluated the differences in hydroxyl free radical (·OH), nitric oxide (NO) and total SOD activity in the different treatment groups. The results demonstrated that RSV infection of A549 cells increased the levels of ·OH and NO, while decreasing the activity of total SOD. Pretreatment of A549 cells with H2O2 prior to RSV infection upregulated the mRNA and protein expression of TLR3 and NF‑κB, and downregulated the mRNA expression of IRF3 and SOD1, as well as the total SOD activity. When the infected cells were pretreated with NAC, the mRNA and protein expression of these genes were reversed. These variations in the TLR3‑mediated signaling pathway molecules suggested that oxidative stress may be a key regulator for TLR3 activation during RSV infection. RSV‑induced oxidative stress may potentially activate TLR3 and enhance TLR3‑mediated inflammation. These results may provide better understanding of the RSV‑induced inflammatory and immune pathways, and may also contribute to the drug development and prevention of human RSV diseases.

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