C16 peptide and angiopoietin-1 protect against LPS-induced BV-2 microglial cell inflammation.

AIMS

Pathological alterations in the brain can cause microglial activation (MA). Thus, inhibiting MA could provide a new approach for treating neurodegenerative disorders.

MAIN METHODS

To investigate the effect of C16 peptide and angiopoietin-1 (Ang1) on inflammation following MA, we stimulated microglial BV-2 cells with lipopolysaccharide (LPS) and used dexmedetomidine (DEX) as a positive control. Specific inhibitors of Tie2, αvβ3 and α5β1 integrins, and PI3K/Akt were applied to investigate the neuron-protective and anti-inflammatory effects and signaling pathway of C16 + Ang1 treatment in the LPS-induced BV-2 cells.

KEY FINDINGS

Our results showed that C16 + Ang1 treatment reduced the microglia M1 phenotype but promoted the microglia M2 phenotype. In addition, C16 + Ang1 treatment suppressed leukocyte migration across human pulmonary microvascular endothelial cells, reduced the levels of pro-inflammatory factors [inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, tumor necrosis factor (TNF-α)], and cellular apoptosis factors (caspase-3 and p53), and decreased lactate dehydrogenase (LDH) release, but promoted anti-inflammatory cytokine (IL-10) expression and cell proliferation in the LPS-activated BV-2 cells. The signaling pathways underlying the neuron-protective and anti-inflammatory effects of C16 + Ang1 may be mediated by Tie2-PI3K/Akt, Tie2-integrin and integrin-PI3K/Akt.

SIGNIFICANCE

The neuron-protective and anti-inflammatory effects of C16 + Ang1 treatment included M1 to M2 microglia phenotype switching, blocking leukocyte transmigration, decreasing apoptotic and inflammatory factors, and promoting cellular viability.