title: Bacterial lipopolysaccharide signaling through Toll-like receptor 4 suppresses asthma-like responses via nitric oxide synthase 2 activity.
abstract: Asthma results from an intrapulmonary allergen-driven Th2 response and is characterized by intermittent airway obstruction, airway hyperreactivity, and airway inflammation. An inverse association between allergic asthma and microbial infections has been observed. Microbial infections could prevent allergic responses by inducing the secretion of the type 1 cytokines, IL-12 and IFN-gamma. In this study, we examined whether administration of bacterial LPS, a prototypic bacterial product that activates innate immune cells via the Toll-like receptor 4 (TLR4) could suppress early and late allergic responses in a murine model of asthma. We report that LPS administration suppresses the IgE-mediated and mast cell-dependent passive cutaneous anaphylaxis, pulmonary inflammation, airway eosinophilia, mucus production, and airway hyperactivity. The suppression of asthma-like responses was not due to Th1 shift as it persisted in IL-12(-/-) or IFN-gamma(-/-) mice. However, the suppressive effect of LPS was not observed in TLR4- or NO synthase 2-deficient mice. Our findings demonstrate, for the first time, that LPS suppresses Th2 responses in vivo via the TLR4-dependent pathway that triggers NO synthase 2 activity.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Dunia
authors.initials: D
authors.lastname: Rodríguez
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Keller
authors.forename: Eliana L
authors.initials: EL
authors.lastname: Faquim-Mauro
authors.forename: Mahasti S
authors.initials: MS
authors.lastname: de Macedo
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Jean
authors.initials: J
authors.lastname: Lefort
authors.forename: B Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D001980:Bronchi / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004789:Enzyme Activation / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000196:embryology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019779:Salmonella enterica / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse