Mitogen-activated protein kinase signaling is involved in nonylphenol-induced proinflammatory cytokines secretion by
Weijia Gu1, Yi Wang1, Zhenmin Qiu1
1Department of Occupational and Environmental Health, School of Public Heath, China Medical University, Shenyang, People's Republic of China.
Abstract:
Microglia (MG) are the key cells involved in the innate immune response in the central nervous system, and their activation has been linked to inflammation and neurotoxicity by the production of proinflammatory cytokines. Recently, researchers have found that nonylphenol (NP), a ubiquitous endocrine disrupting chemical, could impair neurodevelopment and cognitive memory performance. However, whether NP affects the inflammatory responses of MG remains to be elucidated. The aim of this study was to explore the effects of NP on the inflammatory responses of BV2 MG and the underlying mechanisms. Our results showed that NP increased the secretion of interleukin (IL)-6 and IL-1β in BV2 MG. Increased phosphorylation of Akt, JNK and p38 mitogen-activated protein kinase and decreased phosphorylation of ERK were observed in NP-treated MG. The inflammatory transcription factor activator protein 1 was also activated in NP-treated BV2 MG. These results suggest that NP may activate Akt/mitogen-activated protein kinase/activator protein 1 signaling in MG and subsequently increase IL-6 and IL-1β secretion.
Insights
Nonylphenol (NP) exposure activates microglia (MG) inflammatory responses, increasing pro-inflammatory cytokines IL-6 and IL-1β. This occurs via the Akt/mitogen-activated protein kinase/activator protein 1 signaling pathway in the central nervous system.
Area of Science:
- Neuroscience
- Immunology
- Toxicology
Background:
- Microglia (MG) are central nervous system immune cells, crucial for innate immunity.
- Microglia activation produces proinflammatory cytokines, contributing to inflammation and neurotoxicity.
- Nonylphenol (NP), an endocrine disruptor, is known to impair neurodevelopment and memory.
Purpose of the Study:
- To investigate the impact of nonylphenol (NP) on the inflammatory responses of BV2 microglia.
- To elucidate the underlying molecular mechanisms by which NP influences microglia activation.
Main Methods:
- BV2 microglia cells were treated with nonylphenol (NP).
- Cytokine secretion (IL-6, IL-1β) was measured.
- Protein phosphorylation (Akt, JNK, p38 MAPK, ERK) was analyzed.
- Activator protein 1 (AP-1) activation was assessed.
Main Results:
- Nonylphenol (NP) significantly increased the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in BV2 microglia.
- NP treatment led to increased phosphorylation of Akt, JNK, and p38 mitogen-activated protein kinase (MAPK).
- NP exposure resulted in decreased phosphorylation of ERK and activation of the transcription factor activator protein 1 (AP-1).
Conclusions:
- Nonylphenol (NP) provokes inflammatory responses in microglia.
- NP activates the Akt/MAPK/AP-1 signaling pathway in microglia.
- This activation leads to increased secretion of IL-6 and IL-1β, suggesting a role in neuroinflammation.
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