It is well recognized that air pollution is a major public health issue with direct impact on lung health. The source of air pollution and its concentration can vary widely based on climatic conditions and specific emission sources. There are two primary types of air pollution sources: natural and anthropogenic. Natural sources include biomass burning, wildfires, and soil dust. Anthropogenic sources encompass activities such as fossil fuel combustion, heavy industrial processes, agricultural emissions, cigarette smoke, emissions of volatile organic compounds, as well as abrasion derived particles from brake pads and tire wear (Thangavel et al., 2022). A number of toxic compounds from these sources have been identified, including particulate matter (PM), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAHs).

Vulnerable populations, such as children, the elderly, and individuals with pre-existing respiratory conditions, are particularly susceptible to the detrimental effects of air pollution on lung health (Amnuaylojaroen & Parasin, 2024). Understanding the underlying mechanisms linking air pollution to the increased risk of respiratory diseases in vulnerable individuals is essential for developing future strategies and pharmacological interventions to mitigate the public health burden of air pollution. Several studies have demonstrated a strong association between air pollution and various respiratory and lung conditions. Evidence shows that air pollution is linked to the development and exacerbation of asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF) (Collaborators, 2023; Deng et al., 2015). Early life exposure to air pollutants, encompassing prenatal exposure and exposure during the first year of life, has been particularly associated with an increased risk of developing childhood asthma. Pollutants such as PM, NO₂, and O₃ contribute to this increased risk (Zanobetti et al., 2024). Several studies have highlighted the impact of various air pollutants on asthma development, emphasizing the importance of both the source and concentration of pollutants (Dearborn et al., 2023; Deng et al., 2015; Zanobetti et al., 2024).

The adverse health effects of air pollution have been linked to its pollutant components and the presence of toxic substances. Inhaled air pollutants alter various pathways within the pulmonary system, many through receptor-mediated mechanisms. These pollutants, which include a range of substances such as particulate matter, gases, and chemical irritants, can activate specific receptors in the lungs, leading to a cascade of biological responses. Several cellular mechanisms and signaling pathways connect air pollution to respiratory diseases, such as modulation of G protein-coupled receptors (GPCRs) and Toll-like receptors (TLRs), which play crucial roles in regulating pulmonary function and immune responses (Manzano-Covarrubias et al., 2023). GPCRs represent the largest family of transmembrane receptors. Many GPCRs signal by altering cellular levels of the second messengers such as cyclic AMP (cAMP) and calcium (Ca2+). Both second messengers are critically involved in the regulation of airway smooth muscle contraction, inflammatory mediator release, and epithelial barrier function. They regulate ion channels, kinases and transcription factors, leading to the regulation of a vast array of different cellular responses (Manzano-Covarrubias et al., 2023). Impairment of GPCR signaling underlies numerous diseases, such as heart disease, asthma, cancer, and neurological disorders, among others. Given their pivotal role in all physiological systems, GPCRs represent a significant focus of research in pharmacology (Insel et al., 2007; Manzano-Covarrubias et al., 2023; Yang et al., 2021). TLRs belong to a family of receptors that constitute the first line of defense of our immune system responsible for pathogen recognition (Sameer & Nissar, 2021). TLR activation induces intracellular downstream signaling cascades that initiate innate immune responses such as inflammation and antigen-specific adaptive immune responses (Kawasaki & Kawai, 2014).

The lungs are continuously in contact with the external environment, making them particularly vulnerable to environmental pollutants. Exposure to these pollutants is a major risk factor for the development and progression of respiratory diseases, potentially through the modulation of GPCRs and other receptors. In the present review, we summarize what is known about how air pollutants, such as PM, PAHs, cigarette smoke and wood smoke, modulate signaling and function of GPCRs and TLRs in the lung.

Importantly, the characteristics of PM differ depending on its source. PM derived from cigarette smoke contains a complex mixture of combustion byproducts, including high concentrations of organic compounds and reactive chemicals. These differ significantly in composition and physical properties from PM typically found in outdoor environments, such as those from traffic emissions, industrial activity, or natural sources. Such differences in source and chemical profile can lead to distinct biological responses and should be carefully considered when comparing findings across studies. Finally, we discuss potential therapeutic approaches for mitigating the air pollution-associated adverse effects in the lung. Understanding the mechanisms of how air pollutants alter receptor signaling and cellular regulation is crucial for addressing the impact of air pollution on respiratory diseases and for guiding the development targeted therapeutic strategies.