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

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.

• Authors: Miao He, Takamichi Ichinose, Yasuhiro Yoshida, Keiichi Arashidani, Seiichi Yoshida, Hirohisa Takano, Guifan Sun, Takayuki Shibamoto
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 11027 (09 08 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28887522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Particulate Matter
• Tlr2 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Ovalbumin

Topics

• Allergens (administration & dosage, metabolism)
• Animals
• Asthma (chemically induced, pathology)
• Disease Models, Animal
• Mice, Inbred BALB C
• Mice, Knockout
• Myeloid Differentiation Factor 88 (genetics, metabolism)
• Ovalbumin (administration & dosage, metabolism)
• Particulate Matter (administration & dosage, metabolism)
• Pneumonia (chemically induced, pathology)
• Signal Transduction
• Toll-Like Receptor 2 (genetics, metabolism)
• Toll-Like Receptor 4 (genetics, metabolism)