Neuroinflammation is instrumental in neuronal damage observed in various neuropathologies. Thus, understanding pro-inflammatory pathways of human glial cells is important in identifying potential pharmacological strategies to modulate inflammatory signaling in these cells. Microglia-derived cytokines and chemokines are instrumental in neuroinflammation and several proinflammatory mediators activate these cells to include bacterial lipopolysaccharide (LPS) that signals through toll-like receptor 4 (TLR4). Microglial TLR4 signaling is not well studied; therefore, our goal is to investigate the molecular mechanisms of TLR4 microglial signaling, which entailed treatment of human microglial cells (CHME-5) with LPS. LPS induced NF-κB activation, demonstrated by increased NF-κB p65 binding activity and phosphorylated p65 expression in CHME-5 cells. TLR4 expression also increased alongside NF-κB activation. On the other hand, co-exposure to the μ-opioid receptor antagonist, β-funaltrexamine (β-FNA), down-regulated LPS-induced NF-κB activation. To date, our data suggest that the inflammatory actions of microglial TLR4 signaling may be partly due to modulation of NF-κB activation. Thus, we have also initiated studies to elucidate the effects of LPS and β-FNA on other key TLR4 signal transduction proteins. Together, these ongoing studies are expected to further elucidate the mechanisms of LPS-induced TLR4 signaling in human microglia.
- Copyright © 2013 by The American Association of Immunologists, Inc.