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Airway hyperresponsiveness (AHR) is characterized by excessive bronchoconstriction in response to nonspecific stimuli, thereby leading to airway stenosis and increased airway resistance. AHR is recognized as a key characteristic of asthma and is associated with significant morbidity. At present, many studies on the molecular mechanisms of AHR have mainly focused on the imbalance in Th1/Th2 cell function and the abnormal contraction of airway smooth muscle cells. However, the specific mechanisms of AHR remain unclear and need to be systematically elaborated. In addition, the effect of air pollution on the respiratory system has become a worldwide concern. To date, numerous studies have indicated that certain concentrations of fine particulate matter (PM2.5) can increase airway responsiveness and induce acute exacerbation of asthma. Of note, the concentration of PM2.5 does correlate with the degree of AHR. Numerous studies exploring the toxicity of PM2.5 have mainly focused on the inflammatory response, oxidative stress, genotoxicity, apoptosis, autophagy, and so on. However, there have been few reviews systematically elaborating the molecular mechanisms by which PM2.5 induces AHR. The present review separately sheds light on the underlying molecular mechanisms of AHR and PM2.5-induced AHR.

The health risks of air pollutants and ambient particulate matter (PM) are widely known. PM composition and toxicity have shown substantial spatiotemporal variability. Yet, the connections between PM composition and toxicological and health effects are vaguely understood. This is a crucial gap in knowledge that needs to be addressed in order to establish air quality guidelines and limit values that consider the chemical composition of PM instead of the current assumption of equal toxicity per inhaled dose. Here, we demonstrate further evidence for varying toxicological effects of urban PM at equal mass concentrations, and estimate how PM composition and emission source characteristics influenced this variation. We exposed a co-culture model mimicking alveolar epithelial cells and macrophages with size-segregated urban ambient PM collected before, during, and after the Nanjing Youth Olympic Games 2014. We measured the release of a set of cytokines, cell cycle alterations, and genotoxicity, and assessed the spatiotemporal variations in these responses by factorial multiple regression analysis. Additionally, we investigated how a previously identified set of emission sources and chemical components affected these variations by mixed model analysis. PM-exposure induced cytokine signaling, most notably by inducing dose-dependent increases of macrophage-regulating GM-CSF and proinflammatory TNFα, IL-6, and IL-1β concentrations, modest dose-dependent increase for cytoprotective VEGF-A, but very low to no responses for anti-inflammatory IL-10 and immunoregulatory IFNγ, respectively. We observed substantial differences in proinflammatory cytokine production depending on PM sampling period, location, and time of day. The proinflammatory response correlated positively with cell cycle arrest in G1/G0 phase and loss of cellular metabolic activity. Furthermore, PM 0.2 caused dose-dependent increases in sub-G1/G0 cells, suggesting increased DNA degradation and apoptosis. Variations in traffic and oil/fuel combustion emissions contributed substantially to the observed spatiotemporal variations of toxicological responses., (Copyright © 2020. Published by Elsevier Inc.)