Induction of immune tolerance and reduction of aggravated lung eosinophilia by co-exposure to Asian sand dust and ovalbu
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RESEARCH
ALLERGY, ASTHMA & CLINICAL IMMUNOLOGY
Open Access
Induction of immune tolerance and reduction of aggravated lung eosinophilia by co-exposure to Asian sand dust and ovalbumin for 14 weeks in mice Miao He1,4, Takamichi Ichinose1, Seiichi Yoshida1, Hirohisa Takano2, Masataka Nishikawa3, Guifan Sun4 and Takayuki Shibamoto5*
Abstract Background: Atmospheric contamination caused by Asian sand-dust (ASD) storms aggravates asthma in both human adults and children. This study aims to investigate a series of manifestations in allergic airway disease caused by co-exposure to allergens and ASD for 6 weeks and 14 weeks. Methods: CD-1 Mice were instilled intratracheally with 0.1 mg of ASD/mouse four times (6 weeks) or eight times (14 weeks) at 2-week intervals (total dose of 0.4 mg or 0.8 mg/mouse) with or without ovalbumin (OVA). The pathologic changes in the airway, cytological alteration in bronchoalveolar lavage fluid (BALF), and levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice. Results: Four-time co-exposure to OVA and ASD aggravates allergic airway inflammation along with Th2-cytokine IL-13 and eosinophil-relevant cytokine/chemokines IL-5, Eotaxin and MCP-3 in BALF, and fibrous thickening of the subepithelial layer in the airway. On the other hand, eight-time co-exposure attenuates these changes along with a significant increase of TGF-β1 in BALF. Adjuvant effects of ASD toward IgG1 and IgE production in sera were, however, still seen in the eight-time co-exposure. Conclusions: These results indicate that the immune responses in airways are exacerbated by four-time coexposure to ASD with OVA, but that there is a shift to suppressive responses in eight-time co-exposure, suggesting that the responses are caused by TGF-β1-related immune tolerance.
Background Asian sand dust (ASD) storms arise annually from the Gobi Desert, the Taklimakan desert, and loess areas of interior China during the spring season and/or sometimes during the autumn season every year [1]. ASD aerosol spreads through downwind areas, such as East China, the Korean Peninsula, and Japan as well as across the Pacific Ocean to the United States [2-4]. It is also reportedly that ASD transported one full circuit around the globe [5]. Moreover, recent researches point out that * Correspondence: [email protected] 5 Department of Environmental Toxicology, Takayuki Shibamoto, University of California, Davis, CA 95616, USA Full list of author information is available at the end of the article
the frequency of ASD storm increases rapidly after the year of 2000, and ASD storm may enter a new active period [6]. A major public concern on ASD is its potential hazardous-effect toward respiratory diseases in the Eastern Asian countries. ASD aerosol contains various toxic materials, including by-product materials derived from combustion of a fossil fuel like polycyclic aromatic hy− drocarbons (PAHs), sulfate (SO2− 4 ), and nitrate (NO3 ) and microbial agents, such
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