What question did this study set out to answer?

This study aims to explore the effects of distinct chemical fractions of PM2.5 on oxidative potential and inflammation.

March 28, 2026Open Access

Synergistic and antagonistic effects of PM2.5 chemical fractions on oxidative potential, cellular inflammation, and gene expression

GXGuangshan XieHong Kong Baptist University XWXuemei WangHong Kong Baptist University CLChin Wai LeungHong Kong Baptist University

Key Points

This study aims to explore the effects of distinct chemical fractions of PM2.5 on oxidative potential and inflammation.
Analyzed five chemical fractions of PM2.5: water-soluble total, metals, non-metals, lipid-soluble, and total extract.
Conducted oxidative potential analysis using dithiothreitol (DTT) consumption and hydroxyl radical generation measurements.
Assessed gene expression changes associated with inflammation and oxidative stress.
Metals primarily drove DTT consumption, while organics contributed to hydroxyl radical generation.
Water-soluble total fraction induced highest TNF-α secretion and upregulated inflammatory genes.
Synergistic upregulation of Hmox-1 observed between water-soluble metals and non-metal fractions.
Lipid-soluble fraction showed antagonistic effects on TNF-α secretion and oxidative stress gene expression.

Abstract

Long-term exposure to fine particulate matter (PM 2.5 ) is associated with respiratory and cardiovascular diseases. PM 2.5 consists of a complex mixture of organic and inorganic species, with toxicity varying based on its chemical composition, sources, and physicochemical properties. This study investigates the oxidative potential (OP), cellular oxidative stress, and inflammatory response induced by five distinct chemical fractions of urban PM 2.5 : water-soluble total, water-soluble metals, water-soluble non-metal, lipid-soluble, and total PM 2.5 extract. We also analyzed the synergistic and antagonistic interactions among these fractions contributing to overall PM 2.5 toxicity. Comprehensive chemical characterization and OP analysis of PM 2.5 extracts revealed that metals primarily drive dithiothreitol (DTT) consumption, while organics predominantly contribute to hydroxyl radical (∙OH) generation. Notably, high PM 2.5 samples exhibited significant antagonistic interactions between water-soluble metals and organic fractions in the generation of ∙OH. The water-soluble total fraction induced the highest levels of TNF-α secretion and upregulated the expression of genes associated with inflammation and oxidative stress, including Cxcl2 , Hmox-1 , and Cyp1a1 , emphasizing its dominant role in PM 2.5 -induced cytotoxicity. Synergistic upregulation of Hmox-1 expression was observed between water-soluble metals and non-metal fractions, whereas Cxcl2 expression was antagonistically modulated. Conversely, the lipid-soluble fraction exhibited an antagonistic effect on TNF-α secretion and oxidative stress gene expression relative to the water-soluble total fraction. These findings highlight the pivotal role of water-soluble components in PM 2.5 toxicity and provide a comprehensive framework for understanding the individual and combined effects of chemical fractions on PM 2.5 -induced toxicity, which is vital for accurately assessing its impact on human health. • Metals dominate DTT consumption; organics lead ∙OH generation in PM 2.5 • Water-soluble total fraction of PM 2.5 induces highest TNF-α and gene expression • Synergistic Hmox-1 upregulation by metals and organics; antagonistic for Cxcl2 • Lipid-soluble fraction of PM 2.5 shows antagonistic effects on oxidative stress markers • Novel multidimensional approach links PM 2.5 chemical fractions to toxicity outcomes

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