Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway

Nevertheless its mechanism has not been well explained yet, PM2.5 is recognized to exacerbateasthma. In the present study, the roles of toll-like receptor (TLR) 2, TLR4and MyD88, in exacerbationof allergen-induced lung eosinophiliacaused 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 exacerbatedOVA-related lung eosinophilia. This exacerbationincludes increase of IL-5, IL-13, eotaxinand MCP-3; infiltration of eosinophils into the airway submucosa; proliferation of goblet cellsin 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 inflammationin 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 exacerbationof murine lung eosinophilia.