MAPK and NF-κB pathways are involved in bisphenol A-induced TNF-α and IL-6 production in BV2 microglial cells

Area of Science:

• Neuroimmunology
• Endocrinology
• Toxicology

Background:

• Microglial activation and pro-inflammatory cytokine production are implicated in neurodegenerative diseases.
• Bisphenol A (BPA) is an endocrine-disrupting chemical with unclear effects on the central nervous system's immune response.
• The role of BPA in microglial inflammatory action and its underlying mechanisms require investigation.

Purpose of the Study:

• To investigate whether BPA induces inflammatory responses in microglial cells.
• To explore the potential mechanisms, including signaling pathways and receptor involvement, underlying BPA's effects on microglial activation.
• To determine BPA's impact on pro-inflammatory cytokine production in the central nervous system.

Main Methods:

• Utilized the BV2 murine microglial cell line as a model system.
• Examined BPA-induced morphologic changes, cytokine responses, and signaling events using immunofluorescence, real-time PCR, ELISA, and western blot.
• Investigated the roles of estrogen receptor, JNK, ERK, and NF-κB signaling pathways.

Main Results:

• BPA exposure led to increased BV2 cell activation and elevated expression of tumor necrosis factor-α and interleukin 6.
• These BPA-induced inflammatory effects were partially reversed by the estrogen receptor antagonist ICI182780.
• Inhibition of c-Jun N-terminal protein kinase (JNK) but not ERK1/2 demonstrated anti-inflammatory properties against BPA-elicited cytokine responses.
• BPA specifically activated the inflammatory transcription factor NF-κB.

Conclusions:

• BPA can activate microglial cells and promote pro-inflammatory cytokine production.
• Estrogen receptor, JNK, ERK mitogen-activated protein kinase, and NF-κB signaling pathways are involved in BPA's inflammatory effects on microglial cells.
• These findings suggest BPA has functional impacts on microglial activation and neuroinflammation.