Transcriptomics changes and the candidate pathway in human macrophages induced by different PM_2.5 extracts.

Area of Science:

• Environmental Health
• Molecular Toxicology
• Transcriptomics

Background:

• Ambient fine particulate matter (PM2.5) is a global environmental hazard with significant health implications.
• The precise molecular mechanisms and toxic components of PM2.5 remain incompletely understood.
• Investigating PM2.5's impact on cellular pathways is crucial for understanding its toxicity.

Purpose of the Study:

• To elucidate the transcriptomic alterations in macrophages exposed to different PM2.5 extracts.
• To identify key molecular pathways and genes involved in PM2.5 toxicity.
• To explore the differential effects of seasonal PM2.5 components on cellular responses.

Main Methods:

• Utilized RNA sequencing to analyze whole transcriptomic changes in THP-1 derived macrophages.
• Applied bioinformatics analyses including Gene Ontology (GO), KEGG pathway, and protein-protein interaction (PPI) networks.
• Compared the effects of water extracts (WEs) and dichloromethane extracts (DEs) from PM2.5 collected in different seasons.

Main Results:

• PM2.5 water extracts significantly modulated genes and pathways associated with oxidative stress and inflammation.
• PM2.5 dichloromethane extracts specifically impacted cell cycle-related genes and signaling.
• Non-heating season WEs induced higher expression of calcium-associated genes, suggesting enhanced inflammation.
• Heating season DEs exhibited extensive cell cycle pathway dysregulation, potentially due to higher polycyclic aromatic hydrocarbons (PAHs).

Conclusions:

• Water-soluble PM2.5 components induce oxidative stress and inflammation in macrophages.
• Organic PM2.5 components contribute to cell cycle dysregulation, a key factor in PM2.5's biological effects.
• Seasonal variations in PM2.5 composition, including PAHs and metal ions, influence transcriptomic responses.