RKIP suppresses the influenza A virus‑induced airway inflammatory response via the ERK/MAPK pathway

Ye,Jing-Jing; Wei,Si-Liang; Wei,Yuan-Yuan; Zhang,Da-Wei; Sun,Li; Wu,Hui-Mei; Shen,Ji-Long; Yu,Li; Wang,Yong; Fei,Guang-He

doi:10.3892/ijmm.2022.5204

RKIP suppresses the influenza A virus‑induced airway inflammatory response via the ERK/MAPK pathway

Authors:
- Jing-Jing Ye
- Si-Liang Wei
- Yuan-Yuan Wei
- Da-Wei Zhang
- Li Sun
- Hui-Mei Wu
- Ji-Long Shen
- Li Yu
- Yong Wang
- Guang-He Fei
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Affiliations: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Geriatric Respiratory and Critical Care, Anhui Geriatric Institute, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, Anhui 230022, P.R. China
Published online on: November 16, 2022 https://doi.org/10.3892/ijmm.2022.5204
Article Number: 1
Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Raf kinase inhibitor protein (RKIP) is an inflammation‑inhibiting mediator that is involved in several diseases; however, the potential mechanism of action of RKIP on the inflammatory response induced by influenza A virus (IAV) remains unclear. The present study aimed to investigate whether RKIP regulated the inflammatory response via the ERK/MAPK pathway. The present study detected the expression levels of RKIP and alterations in the inflammatory response in human normal bronchial epithelial BEAS‑2B cells, diseased human bronchial epithelial cells and primary human bronchial epithelial cells infected with IAV. Cells were treated with locostatin to inhibit the expression of RKIP. RKIP was overexpressed by lentivirus transduction and the small molecule inhibitor SCH772984 was applied to specifically inhibit activation of the ERK/MAPK pathway. In addition, C57BL/6 mice were infected with IAV to further confirm the role of RKIP in regulation of the inflammatory response via ERK/MAPK in vivo. Western blotting, reverse transcription‑quantitative PCR, ELISA, 5‑ethynyl‑2'‑deoxyuridine assay, immunofluorescence staining, Cell Counting Kit‑8, cell cycle assay, hematoxylin and eosin staining, and immunohistochemistry were used to detect all of the changes. Notably, RKIP attenuated the inflammatory response that was triggered by IAV infection in airway epithelial cells, which was characterized by augmented inflammatory cytokines and cell cycle arrest. Furthermore, the ERK/MAPK pathway was revealed to be activated by IAV infection and downregulation of RKIP aggravated the airway inflammatory response. By contrast, overexpression of RKIP effectively ameliorated the airway inflammatory response induced by IAV. These findings demonstrated that RKIP may serve a protective role in airway epithelial cells by combating inflammation via the ERK/MAPK pathway. Collectively, the present findings suggested that RKIP may negatively regulate airway inflammation and thus may constitute a promising therapeutic strategy for airway inflammatory‑related diseases that are induced by IAV.

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