Air pollution and diseases: signaling, G protein-coupled and Toll like receptors

Abstract

Air pollution is a significant public health issue that impacts lung health, particularly in vulnerable populations such as children, the elderly, and individuals with pre-existing respiratory conditions. Both natural and anthropogenic sources of air pollution give rise to a variety of toxic compounds, including particulate matter (PM), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAHs). Exposure to these pollutants is strongly associated with the development and exacerbation of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Notably, early life exposure to pollutants such as PM, NO₂, and O₃ is linked to an increased risk of childhood asthma. Air pollution can mediate adverse effects through effects on receptor signaling pathways, particularly those involving G-protein coupled receptors (GPCRs) and Toll-like receptors (TLRs). Both of these receptor families play key roles in regulating pulmonary function and immune responses. GPCRs are involved in mediating cellular responses via cyclic AMP (cAMP), calcium and other second messengers, while TLRs initiate immune responses. Understanding how air pollutants and cigarette smoke alter GPCR and TLR function to contribute to lung disease is a critical area of study, as these receptors play central roles in regulating inflammation, immune responses, oxidative stress, airway remodeling and airway tone. Disruption of their signaling by pollutants can exacerbate respiratory conditions such as asthma and COPD. This review explores what is known about how air pollution impacts GPCR and TLR signaling, offers insights into the mechanisms underlying respiratory disease development and highlights potential therapeutic strategies aimed at mitigating the impact of air pollution on lung health.