Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter

Abstract

Air pollution of anthropogenic origin is largely from the combustion of biomass (e.g., wood), fossil fuels (e.g., cars and trucks), incinerators, landfills, agricultural activities and tobacco smoke. Air pollution is a complex mixture that varies in space and time, and contains hundreds of compounds including volatile organic compounds (e.g., benzene), metals, sulphur and nitrogen oxides, ozone and particulate matter (PM). PM_0.1 (ultrafine particles (UFP)), those particles with a diameter less than 100 nm (includes nanoparticles (NP)) are considered especially dangerous to human health and may contribute significantly to the development of numerous respiratory and cardiovascular diseases such as chronic obstructive pulmonary disease (COPD) and atherosclerosis. Some of the pathogenic mechanisms through which PM_0.1 may contribute to chronic disease is their ability to induce inflammation, oxidative stress and cell death by molecular mechanisms that include transcription factors such as nuclear factor κB (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Epigenetic mechanisms including non-coding RNA (ncRNA) may also contribute towards the development of chronic disease associated with exposure to PM_0.1. This paper highlights emerging molecular concepts associated with inhalational exposure to PM_0.1 and their ability to contribute to chronic respiratory and systemic disease.

Keywords: air pollution; aryl hydrocarbon receptor; chronic obstructive pulmonary disease; epigenetics; nuclear factor-κB; particulate matter.

Figure 1

The molecular mechanisms associated with inflammatory and oxidative stress in response to chronic exposure to PM_0.1. PM, particulate matter; ROS, generation of reactive oxygen; JNK, c-Jun kinase; AhR, Aryl hydrocarbon receptor; Nrf2, nuclear factor (erythroid-derived 2)-like 2; ARE, antioxidant response element; XRE, xenobiotic response element; AP-1-RE, AP-1 response element; NF-κB-RE, NF-κB response element; RelA, v-rel avian reticuloendotheliosis viral oncogene homolog A or p65; RelB, reticuloendotheliosis viral oncogene homologue B; NADPH, nicotinamide adenine dinucleotide phosphate-oxidase; Arnt, aryl hydrocarbon receptor nuclear translocator. Solid line: activation; dashed line: translocation; red line: inflammatory/oxidant pathway; red dashed line: anti-inflammatory/ anti-oxidant pathway.

Figure 2

Intersecting pathogenic mechanisms converge to increase susceptibility to developing chronic cardiopumonary diseases assocoated with exposure to PM_0.1.