Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases

Journal of Neuroinflammation

Wei R Chen²  Feifan Zhou¹  Sheng Song¹ 

[1] MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, No. 55 Zhongshan Avenue West, Guangzhou, Tianhe District, 510631, China;Department of Engineering and Physics, University of Central Oklahoma, 100 North University Drive, Edmond, Oklahoma, 73034, USA

关键词: TLR;    LLLT;    Phagocytosis;    Inflammation;    Microglia;   

Others  :  1160248
DOI  :  10.1186/1742-2094-9-219

 received in 2012-04-03, accepted in 2012-08-22,  发布年份 2012

【 摘 要 】

Background

Activated microglial cells are an important pathological component in brains of patients with neurodegenerative diseases. The purpose of this study was to investigate the effect of He-Ne (632.8 nm, 64.6 mW/cm²) low-level laser therapy (LLLT), a non-damaging physical therapy, on activated microglia, and the subsequent signaling events of LLLT-induced neuroprotective effects and phagocytic responses.

Methods

To model microglial activation, we treated the microglial BV2 cells with lipopolysaccharide (LPS). For the LLLT-induced neuroprotective study, neuronal cells with activated microglial cells in a Transwell™ cell-culture system were used. For the phagocytosis study, fluorescence-labeled microspheres were added into the treated microglial cells to confirm the role of LLLT.

Results

Our results showed that LLLT (20 J/cm²) could attenuate toll-like receptor (TLR)-mediated proinflammatory responses in microglia, characterized by down-regulation of proinflammatory cytokine expression and nitric oxide (NO) production. LLLT-triggered TLR signaling inhibition was achieved by activating tyrosine kinases Src and Syk, which led to MyD88 tyrosine phosphorylation, thus impairing MyD88-dependent proinflammatory signaling cascade. In addition, we found that Src activation could enhance Rac1 activity and F-actin accumulation that typify microglial phagocytic activity. We also found that Src/PI3K/Akt inhibitors prevented LLLT-stimulated Akt (Ser473 and Thr308) phosphorylation and blocked Rac1 activity and actin-based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway.

Conclusions

The present study underlines the importance of Src in suppressing inflammation and enhancing microglial phagocytic function in activated microglia during LLLT stimulation. We have identified a new and important neuroprotective signaling pathway that consists of regulation of microglial phagocytosis and inflammation under LLLT treatment. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.

【 授权许可】

   
2012 Song et al.; licensee BioMed Central Ltd.

【 图 表 】

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