Role of TREM1 in the sevoflurane-induced inflammatory activation of microglia in vitro
Chunchun Tang1, Yuhang Zhu1, Dexing Liu1
1Department of Anesthesiology Affiliated Hospital of Zunyi Medical University Zunyi China.
Abstract:
Perioperative neurocognitive disorders (PNDs) are one of the most common complications in perioperative patients, and neuroinflammatory reaction mediated by microglia plays a key role in their formation, but the underlying mechanism remains unknown. Given that the triggering receptor expressed on myeloid cells 1 (TREM1) is a key regulator of inflammation, this study aimed to observe the role of TREM1 on the sevoflurane-induced inflammatory activation in microglia. BV2 microglia were subjected to varying sevoflurane concentrations and durations to assess their viability using CCK8 and the expression of TREM1, iNOS, and ARG using enzyme-linked immunosorbent assays. Additionally, TREM1 knockdown lentivirus was employed to examine its impacts on microglia response to sevoflurane and altered expression of inflammatory markers, IL-1β, TNF-α, TGF-β, IL-10, iNOS, and ARG, as detected using qRT-PCR and immunofluorescence for INOS/Iba-1 and ARG/Iba-1. Our findings underscore the potent inflammatory activation induced by prolonged, high-concentration sevoflurane exposure on microglia. We highlight the potential role of TREM1 as a modulator of microglial polarization and a potential target for the treatment and prevention of sevoflurane-induced PNDs.
Insights
Perioperative neurocognitive disorders (PNDs) involve microglia-driven inflammation. This study reveals Triggering Receptor Expressed on Myeloid cells 1 (TREM1) modulates sevoflurane-induced microglial activation, suggesting TREM1 as a potential therapeutic target for PNDs.
Area of Science:
- Neuroscience
- Immunology
- Anesthesiology
Background:
- Perioperative neurocognitive disorders (PNDs) are common post-surgery complications.
- Microglia-mediated neuroinflammation is implicated in PND pathogenesis, but mechanisms are unclear.
- Triggering Receptor Expressed on Myeloid cells 1 (TREM1) is a key inflammatory regulator.
Purpose of the Study:
- To investigate the role of TREM1 in sevoflurane-induced inflammatory responses in microglia.
- To explore TREM1's impact on microglial polarization and inflammatory marker expression.
Main Methods:
- BV2 microglia were exposed to sevoflurane at varying concentrations and durations.
- Cell viability was assessed (CCK8), and TREM1, iNOS, ARG expression measured (ELISA).
- TREM1 knockdown was performed, and inflammatory markers (IL-1β, TNF-α, TGF-β, IL-10) were analyzed (qRT-PCR, immunofluorescence).
Main Results:
- Prolonged, high-concentration sevoflurane induced significant microglial inflammatory activation.
- TREM1 expression was altered by sevoflurane exposure.
- TREM1 knockdown modulated sevoflurane-induced inflammatory responses and microglial polarization.
Conclusions:
- Sevoflurane triggers potent microglial inflammatory activation, particularly at high concentrations and prolonged durations.
- TREM1 plays a crucial role in modulating microglial polarization during sevoflurane exposure.
- TREM1 represents a potential therapeutic target for preventing and treating sevoflurane-induced PNDs.
