Repeated Lipopolysaccharide Stimulation Induces Cellular Senescence in BV2 Cells

NeuroImmunoModulation - Tập 19 Số 2 - Trang 131-136 - 2012
Hongmei Yu1, Yanmin Zhao1, Xiaoguang Luo2, Yu Feng1, Yan Ren1, Hong Shang2, Zhiyi He1, Xiaomeng Luo3, Shengdi Chen4, Xiyin Wang4
1Neurology, First Affiliated Hospital of China Medical University,
2*Laboratory Medicine and
3Seven-Year Program, China Medical University, Shenyang, and
4Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Tóm tắt

<i>Background and Aim:</i> The dual action of microglia in neurodegenerating diseases has been controversial for some time. Recent studies indicate that microglia senescence might be the key determinant. When microglia age, they function abnormally and fail to respond correctly to stimuli, which eventually promotes neurodegeneration. Accumulating evidence has shown a close relationship between inflammation and aging. Since neuroinflammation is characterized by microglia activation, we assessed if the repeated activation of microglia would lead to senescence. <i>Method:</i> The microglia cell line BV2 was repeatedly stimulated every 48 h with lipopolysaccharide (LPS; 10 ng/ml) and senescence was evaluated by β-galactosidase staining and the presence of senescence-associated heterochromatic foci as well as by cell cycle arrest detection by flow cytometry. The senescence-associated protein p53 was also detected by Western blot. <i>Results:</i> β-Galactosidase staining was barely detectable in control cells, while it tended to increase with repeated LPS stimulation and was positive in most cells after stimulation with LPS 6 times. Similarly, senescence-associated heterochromatic foci were most prominent in cells repeatedly stimulated with LPS, while almost undetectable in control cells or cells receiving a single stimulation. p53 expression was highest in the cells that received LPS stimulation 6 times, and the largest number of cells arrested in the G0/G1 phase was observed in this same group. <i>Conclusion:</i> Microglial cells tend to undergo senescence after repeated activation, implying that microglia senescence may start after multiple inflammatory challenges.

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NeuroImmunoModulation

Tập 19 Số 2

131-136

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