TRP channels and traffic-related environmental pollution-induced pulmonary disease

Abstract

Environmental pollutant exposures are major risk factors for adverse health outcomes, with increased morbidity and mortality in humans. Diesel exhaust (DE) is one of the major harmful components of traffic-related air pollution. Exposure to DE affects several physiological systems, including the airways, and pulmonary diseases are increased in highly populated urban areas. Hence, there are urgent needs to (1) create newer and lesser polluting fuels, (2) improve exhaust aftertreatments and reduce emissions, and (3) understand mechanisms of actions for toxic effects of both conventional and cleaner diesel fuels on the lungs. These steps could aid the development of diagnostics and interventions to prevent the negative impact of traffic-related air pollution on the pulmonary system. Exhaust from conventional, and to a lesser extent, clean fuels, contains particulate matter (PM) and more than 400 additional chemical constituents. The major toxic constituents are nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs). PM and PAHs could potentially act via transient receptor potential (TRP) channels. In this review, we will first discuss the associations between DE from conventional as well as clean fuel technologies and acute and chronic airway inflammation. We will then review possible activation and/or potentiation of TRP vanilloid type 1 (TRPV1) and ankyrin 1 (TRPA1) channels by PM and PAHs. Finally, we will discuss and summarize recent findings on the mechanisms whereby TRPs could control the link between DE and airway inflammation, which is a primary determinant leading to pulmonary disease.

Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air–lung study

“…While there is some absorption throughout the respiratory tract, the primary site of injury is at the terminal bronchioles where particles can be phagocytized by airway macrophages, activate pulmonary nocioceptive fibers or cause direct epithelial damage. 28 Mediated by the formation of reactive oxygen species, this leads to airway and systemic inflammation with ongoing cytokine and chemokine release. Murine models have demonstrated that nitrate exposure causes cellular injury, epithelial proliferation, hyperplasia, inflammation and fibrotic changes.…”

Exposure to indoor endocrine‐disrupting chemicals and childhood asthma and obesity

“…Higher exposure to EDCs is related to lower methylation of TNF‐α 5′ CGI, which is associated with airway inflammation, hyperresponsiveness, the regulation of immune cells and a higher risk of asthma in children . Similar to other air pollutants, EDCs may also stimulate airway C‐fibre sensory nerves, which express transient receptor potential (TRP) cation channels; when exposed to irritants, TRP channels release neuropeptides locally, resulting in cough, airway irritation, mucous secretion and bronchoconstriction mediated by the efferent pathways of the autonomic nervous system . Nassi et al and Cantero‐Recasens et al reported the role of activation and/or increased expression of transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) channels in the pathogenesis of asthma, providing evidence for the role of ANS in the regulation of airway function.…”

Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases

“…Continued exposure to air pollution, toxic chemicals, and particulate matter (PM) causes inflammation of the lungs, leading to cough, asthma, chronic obstructive pulmonary disease (COPD), and other diseases. Studies have indicated that PM activates TRPA1 activity in the respiratory tract, which induces human lung disease ( Deering-Rice et al, 2011 ; Akopian et al, 2016 ). As the level of systemic inflammation increases, the risk of atrial fibrillation in COPD subjects increases ( Grymonprez et al, 2019 ), and there is a negative relationship between the level of asthma control and the increased risk of atrial fibrillation ( Cepelis et al, 2018 ).…”