GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Toxicology

Background:

• Airway inflammation from PM2.5 is crucial in COPD development.
• Aberrant glycogen synthase kinase (GSK)-3β signaling is implicated in inflammatory responses.
• Understanding GSK-3β's role in PM2.5-induced inflammation is critical for COPD research.

Purpose of the Study:

• To investigate the effects of GSK-3β inhibitors on PM2.5-induced inflammatory responses.
• To elucidate the role of the JNK/NF-κB signaling pathway in this process.
• To evaluate specific GSK-3β inhibitors for potential therapeutic applications.

Main Methods:

• Analysis of phosphorylated GSK-3β (p-GSK-3β) in PM2.5-exposed mice via immunohistochemistry.
• Treatment of human bronchial epithelial cells (HBECs) with GSK-3β or JNK inhibitors prior to PM2.5 stimulation.
• Assessment of GSK-3β signaling, JNK/NF-κB activation, and inflammatory cytokine production (HMGB1, IL-6, IL-10) using Western blotting, qRT-PCR, and ELISA.

Main Results:

• PM2.5 exposure induced lung inflammation, increased HMGB1 and IL-6, decreased IL-10, and reduced p-GSK-3β in mice.
• In HBECs, PM2.5 decreased p-GSK-3β, increased p-JNK/JNK ratio, activated NF-κB, and upregulated HMGB1 and IL-6.
• GSK-3β inhibitors (TDZD-8, SB216763) and JNK inhibitor (SP600125) significantly suppressed PM2.5-induced inflammation and NF-κB activation.
• TDZD-8 showed a more pronounced reduction in inflammation-related cytokines compared to SB216763.

Conclusions:

• GSK-3β inhibition mitigates PM2.5-induced airway inflammation in bronchial epithelial cells.
• The JNK/NF-κB signaling pathway is a key mediator of this inflammatory response.
• Targeting GSK-3β presents a potential therapeutic strategy for PM2.5-related respiratory diseases like COPD.