P2X7 is involved in the anti-inflammation effects of levobupivacaine
Ya-Hsien Huang1, Jiin-Cherng Yen2, Jie-Jen Lee3
1Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Background:
We sough to elucidate whether purinergic P2X7 receptor is actively involved in the effects of levobupivacaine on inhibiting microglia activation.
Materials And Methods:
Microglia were treated with lipopolysaccharide (LPS, 50 ng/mL), LPS plus levobupivacaine (50 μM), or LPS plus levobupivacaine plus the P2X7 receptor agonist Bz-ATP (100 μM) and denoted as the LPS, LPS + Levo, and LPS + Levo + Bz-ATP group, respectively. Microglia activation was measured by assaying inflammatory molecules expression. Microglia activation was also measured by assaying neuronal cell viability using coculture of microglia and neurons, as activated microglia may cause neuron injury. We also measured the levels of P2X7 receptor activation in microglia using ethidium uptake assay.
Results:
Our data confirmed the effects of levobupivacaine on inhibiting inflammatory molecules upregulation in activated microglia, as the concentrations of interleukin (IL)-1β, tumor necrosis factor α, IL-6, and macrophage inflammatory protein 2, of the LPS + Levo group were significantly lower than those of the LPS group (all P < 0.05). Moreover, Bz-ATP significantly abrogated the inhibitory effects of levobupivacaine, as concentrations of IL-1β, tumor necrosis factor α, IL-6, and macrophage inflammatory protein 2 of the LPS + Levo + Bz-ATP group were significantly higher than those of the LPS + Levo group (all P < 0.05). In contrast, neuronal cell viability of the LPS + Levo group was significantly higher than those of the LPS and LPS + Levo + Bz-ATP groups (P = 0.012 and 0.002). Moreover, levels of P2X7 receptor activation of the LPS and LPS + Levo + Bz-ATP groups were significantly higher than that of the LPS + Levo group (P = 0.003 and 0.006).
Conclusions:
P2X7 receptor is involved in the effects of levobupivacaine on inhibiting microglial activation.
Insights
Levobupivacaine inhibits microglia activation by reducing inflammatory molecules. The purinergic P2X7 receptor plays a key role in this process, as its activation reverses levobupivacaine
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia activation is implicated in neuroinflammation.
- Levobupivacaine's effects on microglia activation require elucidation.
- The role of the purinergic P2X7 receptor in this context is unknown.
Purpose of the Study:
- To investigate the involvement of the purinergic P2X7 receptor in levobupivacaine's inhibitory effects on microglia activation.
- To assess the impact of levobupivacaine and P2X7 receptor modulation on inflammatory responses and neuronal viability.
Main Methods:
- Microglia were stimulated with lipopolysaccharide (LPS) and treated with levobupivacaine, alone or with a P2X7 receptor agonist (Bz-ATP).
- Inflammatory molecule expression (IL-1β, TNF-α, IL-6, MIP-2) and neuronal cell viability were measured.
- P2X7 receptor activation was assessed using ethidium uptake assays.
Main Results:
- Levobupivacaine significantly reduced inflammatory molecule upregulation in LPS-activated microglia.
- The P2X7 receptor agonist Bz-ATP abrogated levobupivacaine's inhibitory effects.
- Neuronal cell viability was enhanced by levobupivacaine, an effect diminished by Bz-ATP.
- P2X7 receptor activation levels were higher in LPS-stimulated microglia and when P2X7 was co-treated with levobupivacaine and Bz-ATP.
Conclusions:
- The purinergic P2X7 receptor is actively involved in mediating the effects of levobupivacaine on inhibiting microglia activation.
- Targeting the P2X7 receptor may represent a therapeutic strategy in conditions involving neuroinflammation.
Related Concept Videos
01:23Local Anesthetics: Common Agents and Their Applications
Cocaine is an ester of benzoic acid and methylecgogine. It is used to anesthetize and vasoconstrict locally. Currently, it is used primarily for topical applications. It is beneficial for surgeries on the upper respiratory tract, providing anesthesia and shrinking the mucosa. Cocaine in the form of cocaine hydrochloride is...
01:16Local Anesthetics: Clinical Application as Intravenous Regional Anesthesia
One of the advantages of...
01:25Acute Inflammation II: Local and Systemic Effects
01:25Analgesia and Pain Management
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
01:23Local Anesthetics: Mechanism of Action
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...