Polycyclic Aromatic Hydrocarbons from Fine Particulate Matter Induce Oxidative Stress and the Inflammatory Response in Human Vocal Fold Fibroblast Cells

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are toxicants in particulate matter (PM). The vocal fold, part of the larynx and a key structure for voicing, is always in contact with air. In recent epidemic studies, PM was shown to cause laryngitis; however, the basic mechanism has not been evaluated. In the present study, intracellular reactive oxygen species (ROS) and proinflammatory cytokine levels were analyzed after exposing human vocal fold fibroblasts (hVFFs) to PM standard reference material (SRM 2786). Expression levels of the aryl hydrocarbon receptor (AhR) and Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) were also evaluated. PM induced ROS formation and proinflammatory cytokines via the AhR CYP1A1 pathway and caused lipid peroxidation and DNA damage. Blocking AhR or CYP1A1 production using siRNAs significantly decreased ROS production and IL-6 and IL-9 expression in PM-exposed hVFFs, thus protecting the cells against oxidative stress. These results confirm that PAHs in PM play an important role in cell damage and inflammation, confirming a basic pathophysiologic relationship between PM exposure and laryngitis.

Associations between Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Overactive Bladder in US Adults: Data from the National Health and Nutrition Examination Survey 2005–2016

“…Activation of AhR upregulates cytochrome P450 (CYP) metabolizing enzymes that can transform PAHs into quinones, which can be further metabolized into semiquinones [ 18 ]. In this pathway, PAHs can induce reactive oxygen species formation through the AhR-CYP1A1 pathway and cause lipid peroxidation and DNA damage [ 19 , 20 ]. In addition, PAHs can also generate strong pro-inflammatory responses; exposure to PAHs in the air can cause macrophages to release pro-inflammatory cytokines, leading to chronic airway inflammation such as asthma [ 21 ].…”

Association between polycyclic aromatic hydrocarbons and periodontitis: Results from a large population‐based study

“…It is widely recognized that PAHs are AHR activators (Vogel et al, 2020), which are reported to have toxic effects on teeth and hard tissues (Partanen et al, 2004). In addition, other detrimental health effects resulting from the activation of the AHR signalling pathway, particularly in mediating inflammatory responses and oxidative stress, have been widely accepted (Choi & Kim, 2021; Guarnieri et al, 2020). Because the inflammatory response that results in bone resorption is an important mechanism in periodontitis (Sczepanik et al, 2020), it can be speculated that PAHs are potential risk factors that contribute to the development of periodontitis through the mediating effect of the inflammatory response.…”

Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment

“…From observations, blocking of AhR or CYPlal by SiRNA’s decreased the extent of cellular damage. Indicating oxidative pathway in the damage of the DNA [94] .…”