Particulate matter from Saudi Arabia induces genes involved in inflammation, metabolic syndrome and atherosclerosis

Abstract

Airborne particulate matter (PM) exposure is a major environmental health concern and is linked to metabolic disorders, such as cardiovascular diseases (CVD) and diabetes, which are on the rise in the Kingdom of Saudi Arabia. This study investigated changes in mouse lung gene expression produced by administration of PM10 collected from Jeddah, Saudi Arabia. FVB/N mice were exposed to 100 μg PM10 or water by aspiration and euthanized 24 h later. The bronchoalveolar lavage fluid (BALF) was collected and analyzed for neutrophil concentration and tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels. RNA was extracted from lungs and whole transcript was analyzed using Affymetrix Mouse Gene 1.0 ST Array. Mice exposed to PM10 displayed an increase in neutrophil concentration and elevated TNF-α and IL-6 levels. Gene expression analysis revealed that mice exposed to PM10 displayed 202 genes that were significantly upregulated and 40 genes that were significantly downregulated. PM10 induced genes involved in inflammation, cholesterol and lipid metabolism, and atherosclerosis. This is the first study to demonstrate that Saudi Arabia PM10 increases in vivo expression of genes located in pathways associated with diseases involving metabolic syndrome and atherosclerosis.

Fig. 1. TNF-α and IL-6 levels in BALF of mice treated with PM₁₀

Mice were exposed to 100 µg PM₁₀ or distilled water.TNF-α. The average TNF-α levels were 26.2 ± 7.0 and 4.01±1.9 pg/ml in PM₁₀ BALF and control BALF, respectively. TNF- α levels in PM₁₀-treated mice were significantly higher than control mice (p< 0.0012).IL-6. Average IL-6 levels (p< 0.05) were 29.9 ± 9.9 and 4.06 ± 2.7 pg/ml in PM₁₀ BALF and control BALF. IL-6 levels in PM₁₀- treated mice were significantly higher than control mice (p< 0.05).

Fig. 2. Gene expression profiles of PM₁₀-exposed mice

(a) Principal component analysis (PCA) PCA revealed distinct separation between control mice vs. treatment mice Red: PM₁₀; Blue: control (b) Heat Map. Hierarchical cluster analysis of significantly differentially expressed genes in a PM₁₀- treated group compared to an untreated control group. The bar relates the color code to the expression value after quantile normalization and baseline transformation to the median levels of control samples.

Fig. 2. Gene expression profiles of PM₁₀-exposed mice

(a) Principal component analysis (PCA) PCA revealed distinct separation between control mice vs. treatment mice Red: PM₁₀; Blue: control (b) Heat Map. Hierarchical cluster analysis of significantly differentially expressed genes in a PM₁₀- treated group compared to an untreated control group. The bar relates the color code to the expression value after quantile normalization and baseline transformation to the median levels of control samples.

Fig. 3. APOE is a top upstream regulator influencing altered gene expression in PM₁₀-treated mice

APOE was identified as an upstream regulator of many of the genes induced by PM₁₀. Most of the genes affected by this regulator are up-regulated and only a few are down-regulated.