Dexamethasone Reduces Lipopolysaccharide-Caused Inflammation, Apoptosis, and Oxidative Cytotoxicity in Microglia Cells by Attenuating TRPM2 Signaling

Background: Lipopolysaccharide (LPS) production through the upregulation of transient receptor potential melastatin 2 (TRPM2)-caused Ca2+ influx, cytokine production, intracellular reactive oxygen molecules (iROS), and mitochondrial free reactive oxygen radicals (mROS) generation in microglia induces neurodegenerative diseases. As a synthetic glucocorticoid and anesthetic drug, dexamethasone (DEX) inhibits LPS-induced oxidative stress, cytokine production, and apoptosis in brain cells, including mice microglia (BV-2). We aimed to investigate the protective role of DEX on LPS-induced inflammation, apoptosis, and oxidative cytotoxicity in BV-2 cells by attenuating TRPM2 signaling.Methods: We induced five primary groups in the cultured BV-2 cells: control, DEX (100 nM for 24 h), LPS (1 mu g/mL for 24 h), LPS plus DEX, and LPS plus TRPM2 blocker (N-(p-amylcinnamoyl) anthranilic acid or carvacrol). The cell death, oxidants, and Ca2+ analyses of the current study were performed using laser scan confocal microscopy (via fluorescent dyes). A spectrophotometer was used for the lipid peroxidation and antioxidant analyses. An automatic plate reader was used for the apoptosis, cytokine, and caspase analyses. The cell number, debris, and cell viability were determined using a cell counter.Results: The amount of cell death, apoptosis, oxidants (mROS, iROS, and lipid peroxidation), apoptotic indicators (caspase -3, -8, and -9), cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), and interleukin-6 (IL-6)), death cell waste (debris), and Ca2+ were upregulated by LPS incubation, although their amounts were diminished by the DEX and TRPM2 blocker treatments (p <= 0.05). The DEX treatments enhanced the LPS-mediated declines in cell viability, cell number, glutathione, and glutathione peroxidase values (p <= 0.05).Conclusion: The treatment of DEX diminished the LPS-caused inflammatory cytokine, apoptosis, and oxidative stress via TRPM2 attenuation in microglia cells. The DEX may be considered a potential therapeutic way to treat LPS-caused microglia oxidative neuronal injury and neurodegenerative diseases.

Automated summary

The protective role of dexamethasone (DEX) in lipopolysaccharide (LPS)-induced inflammation, apoptosis, and oxidative cytotoxicity in BV-2 cells was investigated by attenuating TRPM2 signaling. The results showed that DEX treatment reduced cell death, apoptosis, oxidants, and cytokine production induced by LPS. Therefore, DEX may be a potential therapeutic approach for neurodegenerative diseases caused by LPS-induced microglia oxidative injury.