Rapamycin inhibits lipopolysaccharide-induced neuroinflammation in vitro and in vivo

Mengke,Na‑Shun; Hu,Bei; Han,Qian‑Peng; Deng,Yi‑Yu; Fang,Ming; Xie,Di; Li,Ang; Zeng,Hong‑Ke

doi:10.3892/mmr.2016.5883

Rapamycin inhibits lipopolysaccharide-induced neuroinflammation in vitro and in vivo

Authors:
- Na‑Shun Mengke
- Bei Hu
- Qian‑Peng Han
- Yi‑Yu Deng
- Ming Fang
- Di Xie
- Ang Li
- Hong‑Ke Zeng
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Affiliations: Faculty of Graduate Studies, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China, Department of Histoembryology, Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: October 25, 2016 https://doi.org/10.3892/mmr.2016.5883
Pages: 4957-4966
Copyright: © Mengke et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alzheimer's disease (AD) is the most common type of progressive neurodegenerative disorder, and is responsible for the most common form of dementia in the elderly. Inflammation occurs in the brains of patients with AD, and is critical for disease progression. In the present study, the effects of rapamycin (RAPA) on neuroinflammation lipopolysaccharide (LPS)-induced were investigated. SH‑SY5Y human neuroblastoma cells were treated with 20 µg/ml LPS and 0.1, 1 or 10 nmol/l RAPA, and were analyzed at various time points (6, 12 and 24 h). The mRNA expression levels of interleukin (IL) 1β, IL6 and hypoxia‑inducible factor 1α (HIF1α) were determined using reverse transcription‑quantitative polymerase chain reaction. The protein expression levels of phosphorylated (p‑)S6, p‑nuclear factor κB (NFκB), p‑inhibitor of NFκB kinase subunit β (IKKβ) and p‑tau protein were measured by western blot analysis. p‑IKKβ, p‑NFκB, p‑S6 and p‑tau were significantly decreased at 6, 12 and 24 h when cells were treated with ≥0.1 nmol/ml RAPA. In addition, female Sprague Dawley rats were intracranially injected with a single dose of 100 µg/kg LPS in the absence or presence of 1 mg/kg RAPA pretreatment. Brain tissues were subjected to immunohistochemical analysis 6‑24 h later, which revealed that the expression levels of HIF1α and p‑S6 in rat cerebral cortex were increased following LPS injection; however, this increase was abrogated by RAPA treatment. RAPA may therefore be considered a potential therapeutic agent for the early or emergency treatment of neuroinflammation.

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