Induction of Proinflammatory Cytokines and C-Reactive Protein in Human Macrophage Cell Line U937 Exposed to Air Pollution Particulates

Abstract

Exposure to particulate matter air pollution causes inflammatory responses and is associated with the progression of atherosclerosis and increased cardiovascular mortality. Macrophages play a key role in atherogenesis by releasing proinflammatory cytokines and forming foam cells in subendothelial lesions. The present study quantified the inflammatory response in a human macrophage cell line (U937) after exposure to an ambient particulate sample from urban dust (UDP) and a diesel exhaust particulate (DEP). The effect of native UDP and DEP was compared with their corresponding organic extracts (OE-UDP/OE-DEP) and stripped particles (sUDP/sDEP) to clarify their respective roles. Exposure to OE-UDP, OE-DEP, UDP, DEP, and 2,3,7,8-tetrachlorodibenzo-p-dioxin led to a greater increase of interleukin (IL)-8, tumor necrosis factor-α, and cyclooxygenase-2 mRNA expression than did the stripped particles, whereas sUDP, sDEP, UDP, and DEP led to a greater production of C-reactive protein and IL-6 mRNA. The particles and the organic extract-induced expression of cyclooxygenase-2 and cytochrome P450 (CYP)1a1 was significantly suppressed by co-treatment with an aryl hydrocarbon receptor (AhR) antagonist, indicating that these effects are mainly mediated by the organic components, which can activate the AhR and CYP1a1. In contrast, the induction of C-reactive protein and IL-6 seems to be a particle-related effect that is AhR independent. The inflammatory response induced by particulate matter was associated with a subsequent increase of cholesterol accumulation, a hallmark of foam cells. Together, these data illustrate the interaction between particulate matter and the inflammatory response as well as the formation of cholesterol-accumulating foam cells, which are early markers of cardiovascular disease.

Effect of air pollution on diabetes and cardiovascular diseases in São Paulo, Brazil

“…Exposure to urban air pollution also causes inflammatory responses being associated with the progression of arteriosclerosis and increased cardiovascular mortality. Macrophages play a key role in arteriogenesis by releasing pro-inflammatory cytokines and forming foam cells in sub-endothelial lesions (30).…”

Useful biomarkers for assessing the adverse health effects of PCBs in allergic children: pediatric molecular epidemiology

“…RNA was reverse transcribed into cDNA using QuantiTect Reverse Transcription (Qiagen). The basic quantitative reverse transcription-polymerase chain reaction (qRT-PCR) protocol was as described in our previous paper [21].…”

Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of bronchial asthma: the importance of gene–gene and gene–environment interactions for disease susceptibility

“…53 For instance, diesel exhaust particles (DEPs) are known to be a major component of suspended atmospheric pollutants and have been shown to initiate and exacerbate airway allergic responses that can directly target multiple airway cells, including epithelial cells, mast cells, macrophages and lymphocytes, and induce the production of cytokines, chemokines and other inflammatory mediators associated with the asthmatic phenotype. [53][54][55] DEPs can initiate and exacerbate airway allergic responses through oxidative stress and reactive oxygen species resulting in an enhanced IgE and histamine production. 8,13,56,57 In addition to this adjuvant effect, DEPs are also known to induce or augment IgE production by acting directly on B cells.…”