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Suppressive effects of levobupivacaine on endotoxin-induced microglial activation
Ya-Hsien Huang1, Jiin-Cherng Yen, Jie-Jen Lee
1Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Background:
We sought to elucidate the effects of levobupivacaine on modulating endotoxin-induced upregulation of inflammatory mediators and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways in activated microglia.
Materials And Methods:
Confluent murine microglia (BV-2) were treated with endotoxin (lipopolysaccharide, 50 ng/mL) or endotoxin plus levobupivacaine (5, 25, or 50 μM) and denoted as the LPS, LPS + L(5), LPS + L(25), and LPS + L(50) groups, respectively. Levobupivacaine was administered immediately after endotoxin. Control groups were run simultaneously.
Results:
The concentrations of inflammatory mediators, including macrophage inflammatory protein-2 (P = 0.023 and 0.016), tumor necrosis factor-α (P = 0.025 and 0.020), interleukin (IL)-1β (P = 0.018 and 0.014), IL-6 (P = 0.029 and 0.023), nitric oxide (P = 0.025 and 0.026), and prostaglandin E2 (P = 0.028 and 0.016) of the LPS + L(25) and LPS + L(50) groups were significantly lower than those of the LPS group. The concentrations of macrophage inflammatory protein-2 (P = 0.035), IL-1β (P = 0.024), nitric oxide (P = 0.031), and prostaglandin E2 (P = 0.036) but not tumor necrosis factor-α and interleukin-6 of the LPS + L(5) group were also significantly lower than those of the LPS group. These data revealed that effects of endotoxin on upregulating inflammatory mediators were inhibited by levobupivacaine. Moreover, effects of endotoxin on activating NF-κB, including inhibitor-κB degradation, NF-κB nuclear translocation, and NF-κB-DNA binding, were also inhibited by levobupivacaine. Similarly, effects of endotoxin on activating MAPKs, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAPK, were also significantly inhibited by levobupivacaine.
Conclusions:
Levobupivacaine significantly inhibited endotoxin-induced upregulation of inflammatory mediators and activation of NF-κB and MAPKs signaling pathways in activated microglia.
Insights
Levobupivacaine effectively reduced inflammatory mediators and inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways in endotoxin-activated microglia, demonstrating its anti-inflammatory potential.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia play a crucial role in neuroinflammation.
- Endotoxin (lipopolysaccharide) is a potent activator of microglia, leading to the release of inflammatory mediators.
- Nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) are key signaling pathways involved in microglial activation and inflammatory responses.
Purpose of the Study:
- To investigate the effects of levobupivacaine on endotoxin-induced inflammatory responses in microglia.
- To determine whether levobupivacaine modulates NF-κB and MAPK signaling pathways in activated microglia.
Main Methods:
- Murine microglia (BV-2 cell line) were stimulated with lipopolysaccharide (LPS).
- Cells were co-treated with varying concentrations of levobupivacaine (5, 25, 50 μM) immediately after LPS exposure.
- Key inflammatory mediators, NF-κB activation (inhibitor-κB degradation, nuclear translocation, DNA binding), and MAPK activation (ERK, JNK, p38) were assessed.
Main Results:
- Levobupivacaine significantly decreased the concentrations of macrophage inflammatory protein-2, tumor necrosis factor-α, IL-1β, IL-6, nitric oxide, and prostaglandin E2 in a dose-dependent manner.
- The drug also inhibited LPS-induced activation of NF-κB signaling, including inhibitor-κB degradation and NF-κB nuclear translocation.
- Levobupivacaine significantly suppressed the activation of MAPKs, including ERK, JNK, and p38.
Conclusions:
- Levobupivacaine exhibits significant anti-inflammatory effects in activated microglia.
- The drug effectively inhibits endotoxin-induced upregulation of inflammatory mediators.
- Levobupivacaine modulates key signaling pathways, NF-κB and MAPKs, involved in microglial activation.
