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Published on: January 7, 2020
PDT-induced HSP70 externalization up-regulates NO production via TLR2 signal pathway in macrophages
Sheng Song1, Feifan Zhou, Wei R Chen
1MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Abstract:
We studied the molecular mechanism underlying PDT-induced apoptosis-dependent macrophage activation, particularly through NO production. We demonstrate that NO production is initially induced by HSP70 on the apoptotic cell surface, and is further enhanced by macrophage phagocytosis. Additionally, we found that apoptotic cells, through TLR2, could activate PI3K, and this could be either dependent or independent of the activation of MyD88. These results reveal a novel pathway linking innate immune signalling to apoptotic cells and point at HSP70 as an important antitumor immunostimulant. They also indicate that PDT-induced apoptosis has an important role in macrophage innate immunity.
Insights
Photodynamic therapy (PDT) triggers macrophage activation via nitric oxide (NO) production, initially by heat shock protein 70 (HSP70) on apoptotic cells, enhanced by phagocytosis. This reveals a novel innate immunity pathway.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Photodynamic therapy (PDT) induces apoptosis, a process that can influence the immune system.
- Macrophage activation is crucial for innate immunity and tumor surveillance.
- Heat shock protein 70 (HSP70) is known to be released from stressed cells.
Purpose of the Study:
- To elucidate the molecular mechanisms of macrophage activation following PDT-induced apoptosis.
- To investigate the role of nitric oxide (NO) production in this process.
- To identify key signaling pathways and molecules involved in the interaction between apoptotic cells and macrophages.
Main Methods:
- Analysis of NO production in response to apoptotic cells.
- Investigation of HSP70's role on the surface of apoptotic cells.
- Assessment of macrophage phagocytosis of apoptotic cells.
- Exploration of Toll-like receptor 2 (TLR2) and MyD88-dependent/independent pathways in PI3K activation.
Main Results:
- PDT-induced apoptosis leads to NO production, initially mediated by surface-expressed HSP70 on apoptotic cells.
- Macrophage phagocytosis further enhances NO production.
- Apoptotic cells activate PI3K signaling in macrophages via TLR2, independent of MyD88 in some cases.
- A novel pathway linking innate immune signaling to apoptotic cells was identified.
Conclusions:
- HSP70 on apoptotic cells is an early inducer of NO production, acting as an immunostimulant.
- PDT-induced apoptosis plays a significant role in activating macrophage-mediated innate immunity.
- The findings reveal a new pathway involving TLR2, PI3K, and potentially MyD88 in immune response to apoptotic cells.
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