Abstract
Nevertheless its mechanism has not been well explained yet, PM2.5 is recognized to exacerbate asthma. In the present study, the roles of toll-like receptor (TLR) 2, TLR4 and MyD88, in exacerbation of allergen-induced lung eosinophilia caused by urban PM2.5 was investigated. TLR2-, TLR4-, MyD88-deficient and WT BALB/c mice were intratracheally challenged with PM2.5 +/− ovalbumin (OVA) four times at 2-week intervals. PM2.5 increased neutrophil numbers and KC in bronchoalveolar lavage fluid and caused slight peribronchiolar inflammation in WT mice. However, these changes were attenuated, but not completely suppressed in gene-deficient mice, especially in MyD88−/− mice. In WT mice, PM2.5 + OVA exacerbated OVA-related lung eosinophilia. This exacerbation includes increase of IL-5, IL-13, eotaxin and MCP-3; infiltration of eosinophils into the airway submucosa; proliferation of goblet cells in the airway epithelium; and the production of antigen-specific IgE and IgG1 in serum. All these effects were stronger in TLR2−/− mice than in TLR4−/− mice. In MyD88−/− mice, this pro-inflammatory mediator-inducing ability was considerably weak and lung pathology was negligible. These results suggest that urban PM2.5 may exacerbate allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway. PM2.5-bound trace microbial elements, such as lipopolysaccharide may be a strong candidate for exacerbation of murine lung eosinophilia.
Highlights
High concentrations of atmospheric particulate matter less than 2.5μm in diameter (PM2.5) are common in Asian countries, especially in some Chinese megacities, and various respiratory health problems have become coincident with this[1, 2]
In our previous work using a murine asthma model, we have shown that urban dust collected from the air in Beijing, China exacerbated ovalbumin (OVA)-associated murine lung eosinophilia[17], as did PM2.5 collected from the air in Shenyang, China[15, 16] and PM2.5-rich dust collected from the air in Fukuoka, Japan[18]
We have recently reported that Myeloid differentiation factor 88 (MyD88) downstream of TLR2 and TLR4 is a key protein in OVA-induced exacerbation of murine lung eosinophilia by Asian sand dust[22]
Summary
High concentrations of atmospheric particulate matter less than 2.5μm in diameter (PM2.5) are common in Asian countries, especially in some Chinese megacities, and various respiratory health problems have become coincident with this[1, 2]. Acute exacerbations are the most clinically significant feature of asthma. They are represented by increase of distal eosinophilic airway inflammation associated with exaggeration of symptoms, such as cough, chest tightness and dyspnoea[5]. In our previous work using a murine asthma model, we have shown that urban dust collected from the air in Beijing, China exacerbated ovalbumin (OVA)-associated murine lung eosinophilia[17], as did PM2.5 collected from the air in Shenyang, China[15, 16] and PM2.5-rich dust collected from the air in Fukuoka, Japan[18]. We have recently reported that MyD88 downstream of TLR2 and TLR4 is a key protein in OVA-induced exacerbation of murine lung eosinophilia by Asian sand dust[22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
