Insights in particulate matter‐induced allergic airway inflammation: Focus on the epithelium

Abstract

Outdoor air pollution is a major environmental health problem throughout the world. In particular, exposure to particulate matter (PM) has been associated with the development and exacerbation of several respiratory diseases, including asthma. Although the adverse health effects of PM have been demonstrated for many years, the underlying mechanisms have not been fully identified. In this review, we focus on the role of the lung epithelium and specifically highlight multiple cytokines in PM-induced respiratory responses. We describe the available literature on the topic including in vitro studies, findings in humans (ie observations in human cohorts, human controlled exposure and ex vivo studies) and in vivo animal studies. In brief, it has been shown that exposure to PM modulates the airway epithelium and promotes the production of several cytokines, including IL-1, IL-6, IL-8, IL-25, IL-33, TNF-α, TSLP and GM-CSF. Further, we propose that PM-induced type 2-promoting cytokines are important mediators in the acute and aggravating effects of PM on airway inflammation. Targeting these cytokines could therefore be a new approach in the treatment of asthma.

Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs

“…This may be a plausible mechanism underlying an epidemiologic association between TRAP exposure and non‐allergic asthma . Injury of airway epithelia by TRAP, for example, DEPs or ozone, can trigger the release of various types of cytokines, including IL‐1, IL‐8, IL‐33, TNF‐α, TSLP and GM‐CSF . Type 2‐promoting cytokines, such as IL‐33 and TSLP, have been shown to activate type‐2 innate lymphoid cells (ILC2s) and initiate airway eosinophilia .…”

Environmental exposures and mechanisms in allergy and asthma development

“…Meta-analyses of American and European cohorts observed substantial heterogeneity across studies that limited the ability to draw conclusions related to diverse definitions in exposure (land-use regression/ dispersion models and roadway proximity) and outcomes (asthma, wheeze, allergic sensitization), and unmeasured confounding of other factors (environmental pollens, fungal spores, climate; socioeconomic) and their complex interactions that drive allergic disease and modify the effects of TRAP exposure (103, 108). Several mechanisms contribute to TRAP-induced allergic disease development and exacerbation, including oxidative stress, altered barrier integrity, and induction of inflammation (14,95,121). Interpretations from mouse studies of TRAP depend on the nature of the traffic pollutant studied.…”

“…The nature of PM-induced inflammation is context dependent. In cultured human epithelial cells, DEP exposure leads to NF-κB activation and transcription of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and neutrophil chemokines such as IL-8 (121,128). Accordingly, acute exposure to DEPs generated an inflammatory response dominated by neutrophils in healthy adults but no changes in lung function (131,132).…”

IL‐33 signalling contributes to pollutant‐induced allergic airway inflammation

“…Asthma has been defined as a heterogeneous disease, with multiple phenotypes that are distinguished based on the patient's clinical characteristics and inflammatory profile. 5,6 Interleukin (IL)-33 plays a key role in bridging innate and adaptive immune responses and contributes to the regulation of tissue homeostasis, injury and repair. 3,4 The airway epithelium is continuously exposed to inhaled environmental triggers.…”

“…It acts not only as a passive barrier but is also actively involved in respiratory defence through pro-inflammatory cytokine production. 5,6 Interleukin (IL)-33 plays a key role in bridging innate and adaptive immune responses and contributes to the regulation of tissue homeostasis, injury and repair. IL-33 has multiple bioactive forms: a full-length and several more potent cleaved forms.…”