Loss of PP4 contributes to diesel exhaust particles-induced epithelial barrier integrity disruption and alarmins release

To the Editor,

Airway epithelial cells (AECs) represent the very first line of defense against the penetration of environmental agents, such as pollutants, into the human body.1 Increasing evidence has revealed that exposure to diesel exhaust particles (DEPs), which are major contributors to near-road traffic-related air pollution, is associated with exacerbation of allergic asthma. Allergic asthma is characterized by aberrations in the epithelial barrier and aggravated type 2 helper T (Th2) cell responses which are attributed to the dysregulated release of epithelium-derived alarmins.2, 3 The epithelial barrier is tightly regulated by phosphorylation/dephosphorylation processes,4 but the cross-talk between protein phosphatases and environmental pollution remains unknown. In this study, we first examined the expression levels of the PP2A subfamily (including PP2A, PP4, and PP6) in response to DEP. As shown in Figure 1A,B, DEP significantly decreased PP4 mRNA and protein levels in cultured BEAS-2B cells in a concentration-dependent manner. However, the expression levels of PP2A and PP6 were not affected (Figure S1). Furthermore, PP4 expression was dramatically decreased mainly in the airway epithelium in a real-world near-roadway air-pollution rat model5 after 6 months of exposure (Figure 1C,D).