Expression of TNF‑α and IL‑β can be suppressed via the PPAR‑γ/mTOR signaling pathway in BV‑2 microglia: A potential anti‑inflammation mechanism

Zhao,Jian‑Lan; Wei,Chen; Xiao,Xiao; Dong,Yin‑Hui; Tan,Bo; Yu,Jian; Chen,Gong; Yuan,Qiang; Du,Zhuo‑Ying; Sun,Yi‑Rui; Hu,Jin; Xie,Rong

doi:10.3892/mmr.2020.11418

Expression of TNF‑α and IL‑β can be suppressed via the PPAR‑γ/mTOR signaling pathway in BV‑2 microglia: A potential anti‑inflammation mechanism

Authors:
- Jian‑Lan Zhao
- Chen Wei
- Xiao Xiao
- Yin‑Hui Dong
- Bo Tan
- Jian Yu
- Gong Chen
- Qiang Yuan
- Zhuo‑Ying Du
- Yi‑Rui Sun
- Jin Hu
- Rong Xie
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Affiliations: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: August 5, 2020 https://doi.org/10.3892/mmr.2020.11418
Pages: 3559-3565

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Abstract

Currently, microglia are considered as crucial factors in suppressing inflammatory reactions, but the specific molecular mechanism remains unknown. To elucidate whether peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) can inhibit neuroinflammatory cytokine expression via the mTOR signal pathway, the BV‑2 cell line was incubated with lipopolysaccharide (10 mM/ml) to induce an inflammatory injury. PPAR‑γ was activated by rosiglitazone, and was inhibited by GW9662. The mTOR signal pathway was activated by phosphatidic acid (P.A.), while it was inhibited by rapamycin. Western blotting and reverse transcription‑quantitative PCR were used to evaluate the expression levels of PPAR‑γ/mTOR signal pathway related proteins and neuroinflammatory cytokines, including NF‑κB, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β. When treated with P.A., the expression levels of phosphorylated (p)mTOR and p‑ribosomal protein S6 kinase (pS6K) were significantly increased and the expression levels of TNF‑α and IL‑1β were significantly lower. However, the expression of PPAR‑γ was similar in P.A. treated cells and cells treated with rapamycin. When PPAR‑γ was activated, pmTOR and pS6K protein expression levels were significantly decreased, and the mRNA expression levels of TNF‑α and IL‑1β were significantly reduced, but this inhibition could be alleviated by administrating GW9662. Collectively, it was indicated that the mTOR signal pathway may be located downstream of PPAR‑γ. Furthermore, neuroinflammatory reactions could be inhibited via the activation of PPAR‑γ by suppressing the mTOR signal pathway in microglia.

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