Exposure to PM2.5 induces aberrant activation of NF-κB in human airway epithelial cells by downregulating miR-331...

Area of Science:

• Environmental Health
• Molecular Biology
• Cell Biology

Background:

• Particulate matter (PM2.5) exposure causes airway epithelial injury via reactive oxygen species (ROS) and pro-inflammatory cytokine release.
• The precise molecular mechanisms of PM2.5 toxicity remain incompletely understood.

Purpose of the Study:

• To elucidate the role of microRNA-331 (miR-331) in PM2.5-induced airway epithelial cell injury.
• To investigate the signaling pathways involved in PM2.5-mediated changes in miR-331 expression and NF-κB activation.

Main Methods:

• Exposure of human airway epithelial Beas-2B (B2B) cells to PM2.5.
• Assessment of nuclear factor kappa B (NF-κB) signaling activation, including p65 nuclear translocation.
• Measurement of miR-331 and inhibitor of NF-κB kinase beta (IKK-β) expression.
• Luciferase reporter assays to confirm miR-331 targeting of IKK-β.
• Inhibition and overexpression studies of ROS, PI3K/Akt, miR-331, and IKK-β.

Main Results:

• PM2.5 exposure induced sustained NF-κB activation and decreased miR-331 expression in B2B cells.
• The reduction in miR-331 was linked to ROS and the phosphoinositide 3-kinase (PI3K)/Akt pathway.
• miR-331 overexpression attenuated PM2.5-induced NF-κB activation and pro-inflammatory cytokine (IL-6, IL-8) production.
• miR-331 directly targets IKK-β, inhibiting its expression and subsequently reducing NF-κB activation.

Conclusions:

• PM2.5 exposure decreases miR-331 expression through the ROS/PI3K/Akt pathway, leading to increased IKK-β and sustained NF-κB activation.
• This mechanism contributes to airway epithelial injury caused by PM2.5.
• Findings offer insights into PM2.5 toxicity mechanisms and potential therapeutic targets.