Resveratrol attenuates IL‑33‑induced mast cell inflammation associated with inhibition of NF‑κB activation and the P38 signaling pathway

Xu,Yundan; Liu,Qiang; Guo,Xiaohong; Xiang,Lei; Zhao,Gang

doi:10.3892/mmr.2020.10952

Resveratrol attenuates IL‑33‑induced mast cell inflammation associated with inhibition of NF‑κB activation and the P38 signaling pathway

Authors:
- Yundan Xu
- Qiang Liu
- Xiaohong Guo
- Lei Xiang
- Gang Zhao
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Affiliations: Department of Medical Biology, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China
Published online on: January 20, 2020 https://doi.org/10.3892/mmr.2020.10952
Pages: 1658-1666

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Abstract

Resveratrol (RSV), a natural polyphenol found in grapes and other herbal plants, has been reported to possess anti‑inflammatory, anti‑oxidative and anti‑proliferative activities. The aim of the present study was to investigate the effect of RSV on interleukin (IL)‑33‑induced inflammatory responses in mast cells and identify the underlying molecular mechanisms. Rat basophilic leukemia (RBL‑2H3) cells were stimulated with IL‑33 in the presence or absence of RSV. MTT, ELISA, reverse transcription‑quantitative PCR and western blot analyses were then performed in order to assess cytotoxicity, inflammatory cytokine production, suppression of tumorigenicity 2 receptor expression, protein expression involved in mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB signaling, respectively. Finally, rats were used to determine the biological effect of RSV in vivo. The results revealed that RSV inhibited cell viability and increased cytotoxicity in a dose‑dependent manner. Medium concentration of RSV (10 µM) treatment attenuated inflammatory cytokine production, such as IL‑6, IL‑13, tumor necrosis factor‑α and monocyte chemotactic protein‑1, and curbed IL‑33‑induced enhancement of immunoglobulin E‑mediated responses in RBL‑2H3 cells, which were associated with the suppression of NF‑κB‑mediated transcription and inhibition of P38 phosphorylation in response to IL‑33 stimulation, but not extracellular signal regulated kinase or JNK. Notably, RSV application also decreased the levels of inflammatory cytokines in rats induced by IL‑33 injection, which was similar to the anti‑inflammatory effect in vitro. The data from the present study demonstrated that RSV played a regulatory role in antagonizing the effects of IL‑33 on mast cells both in vitro and in vivo, suggesting that it has therapeutic potential in IL‑33‑mediated inflammatory diseases that are associated with mast cells.

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