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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
NF-κB/ROS and ERK pathways regulate NLRP3 inflammasome activation in Listeria monocytogenes infected BV2 microglia
Lin Yuan1,2, Yurong Zhu1,3, Shuang Huang1
1School of Medicine, Jiangsu University, Zhenjiang, 212013, P. R. China.
Abstract:
Listeria monocytogenes is a food-borne pathogen responsible for neurolisteriosis, which is potentially lethal in immunocompromised individuals. Microglia are the main target cells for L. monocytogenes in central nervous system (CNS). However, the precise mechanisms by which they trigger neuroinflammatory processes remain unknown. The BV2 microglial cell line and a murine model of L. monocytogenes infection were used for experiments in this study. Listeria monocytogenes induced pyroptosis and nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome activation in BV2. Pharmacological inhibition of the NLRP3 inflammasome attenuated L. monocytogenes-induced pyroptosis. Moreover, inhibition of nuclear factor kappa-B (NF-κB) and extracellular regulated protein kinases (ERK) pathways induced a decrease in caspase1 activation and mature IL-1β-17 secretion. Our collective findings support critical involvement of the NLRP3 inflammasome in L. monocytogenes-induced neuroinflammation and, to an extent, ROS production. In addition, ERK and NF-κB signaling play an important role in activation of the NLRP3 inflammasome, both in vitro and in vivo.
Insights
Listeria monocytogenes triggers neuroinflammation via NLRP3 inflammasome activation in microglia. Inhibiting this pathway, along with NF-κB and ERK signaling, reduces pyroptosis and IL-1β secretion, offering therapeutic insights.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Listeria monocytogenes is a food-borne pathogen causing potentially lethal neurolisteriosis, particularly in immunocompromised individuals.
- Microglia are the primary targets of L. monocytogenes within the central nervous system (CNS), but the mechanisms driving neuroinflammation are not fully understood.
Purpose of the Study:
- To investigate the role of the NLRP3 inflammasome in L. monocytogenes-induced neuroinflammation in microglia.
- To elucidate the involvement of NF-κB and ERK signaling pathways in this process.
Main Methods:
- Experiments utilized the BV2 microglial cell line and a murine model of L. monocytogenes infection.
- Pharmacological inhibition of the NLRP3 inflammasome, NF-κB, and ERK pathways was employed.
- Assays measured pyroptosis, caspase-1 activation, IL-1β secretion, and ROS production.
Main Results:
- L. monocytogenes infection activated pyroptosis and the NLRP3 inflammasome in BV2 microglia.
- Inhibition of the NLRP3 inflammasome significantly reduced L. monocytogenes-induced pyroptosis.
- Inhibition of NF-κB and ERK pathways decreased caspase-1 activation and IL-1β secretion, indicating their role in NLRP3 inflammasome activation.
Conclusions:
- The NLRP3 inflammasome is critically involved in L. monocytogenes-induced neuroinflammation and reactive oxygen species (ROS) production.
- ERK and NF-κB signaling pathways are essential for the activation of the NLRP3 inflammasome during L. monocytogenes infection, both in vitro and in vivo.
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