Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Anti-Inflammatory Effect of Alpha7 Nicotinic Acetylcholine Receptor Modulators on BV2 Cells

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Effector and regulatory T cells in patients with acute optic neuritis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

OBJECTIVE: The development of neuroinflammation shares numerous risk factors and involves many complex interactions which contribute to disease pathology. An important cell type in neuroinflammation is the active microglia cell - the resident immune cell of the CNS. There is increasing need to understand how these pathways related to neuroinflammation work and how they can be regulated. Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated receptors and widely distributed in the brain. The α7 nAChR is a penta-homomeric receptor and is one of the nAChRs expressed in microglia. This study was first designed to characterize the effects of lipopolysaccharide (LPS) on BV2 culture cells, a cell line of murine microglia origin, on release of inflammatory markers and to characterize the inhibitory effects of α7 nAChR modulators in these cells.

METHODS: First, the BV2 cell cultures were functionally validated by exposing them to LPS for 4-24 h and then examining the release of tumor necrosis factor-alpha (TNF-α) using ELISA and nitric oxide (NO) release using the Griess assay, respectively. Next, α7 nAChR modulators with different pharmacological profiles were applied dose-dependently to study their effects on LPS-induced release of NO and TNF-α.

RESULTS: The time-course and dose-response curve revealed that LPS dose-dependently activated (EC50 = 2.5 ng/mL) BV2 cells releasing TNF-α at 4 h, followed by release of NO that occurred first at 8-h time point. The α7 nAChR subunit mRNA was identified in the BV2 cells. The pharmacology studies showed the α7 nAChR selective modulators NS6740 and TQS reduced NO and cytokine release from BV2 cell cultures.

CONCLUSION: We here identified the dose- and time-dependent effects of LPS in BV2 cell cultures on several inflammatory readouts and showed that α7 nAChR modulators with little or no ion channel activity inhibited this anti-inflammatory mechanism.

Original languageEnglish
JournalNeuroImmunoModulation
Volume27
Issue number4
Pages (from-to)194-202
Number of pages9
ISSN1021-7401
DOIs
Publication statusPublished - Mar 2021

Bibliographical note

© 2021 S. Karger AG, Basel.

    Research areas

  • Animals, Anti-Inflammatory Agents, Lipopolysaccharides/pharmacology, Mice, Microglia/metabolism, Tumor Necrosis Factor-alpha/metabolism, alpha7 Nicotinic Acetylcholine Receptor, Alp, BV2 cell cultures, Inflammation, ha7 nicotinic acetylcholine receptor, Microglia

ID: 70647112