Open AccessExpression 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
Author(s) -
JianLan Zhao,
Wei Chen,
Xiao Xiao,
Yinhui Dong,
Bo Tan,
Jian Yu,
Gong Chen,
Qiang Yuan,
Zhuoying Du,
Yirui Sun,
Jin Hu,
Rong Xie
Publication year - 2020
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2020.11418
Subject(s) - pi3k/akt/mtor pathway , peroxisome proliferator activated receptor , signal transduction , ribosomal s6 kinase , p70 s6 kinase 1 , tumor necrosis factor alpha , ribosomal protein s6 , microbiology and biotechnology , microglia , cytokine , biology , inflammation , protein kinase b , cancer research , receptor , chemistry , endocrinology , immunology , biochemistry
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.