title: Dose-dependent immunomodulating effects of endotoxin in allergic airway inflammation.
abstract: How very high exposure levels to endotoxin in a farming environment provide protection against respiratory allergic symptoms and low-to-moderate levels of endotoxin in urban homes promote allergic response is unclear. Dose-specific bacterial endotoxin or LPS-induced tolerance mechanisms can affect lung inflammations, coupled with the Th2 immune responses. Here, we explored the effects of intranasal exposure of LPS at two different doses (based on occupational exposures during handling of agricultural wastes) in OVA-sensitized allergic wild type (WT) and TLR4-KO mice, particularly, with respect to Th2 cytokines and Tregs level. Low-dose LPS (100 ng) exposure prohibited airway tolerance and failed to generate T-cell-dependent protection against lung inflammations in allergic mice. Furthermore, low Tregs at the inflammatory site and induced Th2 cytokines, as well as IL-6 and IL-25, suggested that low-dose LPS might be associated with the suppression of tolerance mechanisms. In contrast, high-dose LPS (20 µg) favored the suppression of Th2 cytokines, IL-6 and IL-25, but failed to induce Th1 cytokines (e.g. IFN-γ). Our results suggest that low-dose LPS can enhance airway allergic inflammation through failing of antigen-dependent immune regulatory homeostasis. The exposure levels of LPS can determine the generation of inflammatory responses in airway allergy.
authors.affiliation: 1 Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.|2 Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.affiliation: 3 Department of Epidemiology & Environmental Health Sciences, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA.
authors.forename: Atin
authors.initials: A
authors.lastname: Adhikari
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D000067565:Farmers; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016273:Occupational Exposure; D011014:Pneumonia / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058408:Th1-Th2 Balance; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: LPS; Tregs; allergy; foxp3