Related Experiment Videos
NF-kappaB modulates lipopolysaccharide-induced microglial nerve growth factor expression
K Heese1, B L Fiebich, J Bauer
1Department of Physiology, University of Basel, Vesalianum, Switzerland.
Abstract:
Microglia/brain macrophages activated in response to injury, infection, or inflammation of the central nervous system (CNS) mediate both neurotoxic and neurotrophic activities. Although the cytotoxic effects of microglia have been analyzed in detail, little is known about the signaling pathways involved in microglial neurotrophin expression. Using purified rat microglial cell cultures, the effects of inflammatory agents such as lipopolysaccharide (LPS) on microglial nerve growth factor (NGF) expression were studied. Application of LPS (0.1-100 ng/ml) induced a rapid (2-4 h), dose-dependent increase in NGF mRNA expression followed by enhanced release of NGF protein within 24 h. To determine whether the transcription factor NF-kappaB, known to be stimulated in activated microglia, is involved in inflammatory mediator-induced NGF expression, we used the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC). Addition of PDTC (100 microM) to microglia completely abolished LPS-induced NGF synthesis, suggesting a key role for NF-kappaB in microglial NGF expression by inflammatory mediators. In conclusion, NF-kappaB-controlled NGF expression by activated microglia appears to contribute to the cross-talk between the immune and nervous systems during inflammation in the CNS.
Insights
Activated microglia release nerve growth factor (NGF) via the NF-kappaB pathway. This process is crucial for communication between the immune and nervous systems during central nervous system inflammation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, play dual roles in neuroinflammation, exhibiting both harmful and helpful effects.
- While microglial cytotoxicity is well-studied, the signaling pathways governing their neurotrophic factor production remain largely unknown.
Purpose of the Study:
- To investigate the signaling mechanisms underlying nerve growth factor (NGF) expression in activated microglia.
- To determine the role of the transcription factor NF-kappaB in inflammatory mediator-induced NGF production by microglia.
Main Methods:
- Utilized primary rat microglial cell cultures exposed to lipopolysaccharide (LPS), a potent inflammatory agent.
- Assessed NGF mRNA and protein levels following LPS stimulation.
- Employed the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) to probe the involvement of this transcription factor.
Main Results:
- Lipopolysaccharide (LPS) treatment dose-dependently increased both NGF mRNA and protein levels in microglia.
- NGF expression was rapidly induced by LPS within 2-4 hours, with enhanced protein release observed at 24 hours.
- Inhibition of NF-kappaB with PDTC completely blocked LPS-induced NGF synthesis, confirming NF-kappaB's critical role.
Conclusions:
- NF-kappaB signaling is essential for inflammatory mediator-induced NGF expression in activated microglia.
- This NF-kappaB-dependent NGF production by microglia contributes to neuro-immune system communication during central nervous system inflammation.