title: Activating transcription factor 3 is a negative regulator of allergic pulmonary inflammation.
abstract: We recently demonstrated the pivotal role of the transcription factor (TF) activating TF 3 (ATF3) in dampening inflammation. We demonstrate that ATF3 also ameliorates allergen-induced airway inflammation and hyperresponsiveness in a mouse model of human asthma. ATF3 expression was increased in the lungs of mice challenged with ovalbumin allergen, and this was associated with its recruitment to the promoters of genes encoding Th2-associated cytokines. ATF3-deficient mice developed significantly increased airway hyperresponsiveness, pulmonary eosinophilia, and enhanced chemokine and Th2 cytokine responses in lung tissue and in lung-derived CD4(+) lymphocytes. Although several TFs have been associated with enhanced inflammatory responses in the lung, ATF3 attenuates the inflammatory responses associated with allergic airway disease.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98103, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gilchrist
authors.forename: William R
authors.initials: WR
authors.lastname: Henderson
authors.forename: April E
authors.initials: AE
authors.lastname: Clark
authors.forename: Randi M
authors.initials: RM
authors.lastname: Simmons
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Smith
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000276:immunology*; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011657:Pulmonary Eosinophilia / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D051700:Activating Transcription Factor 3; D000485:Allergens; D018925:Chemokines; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D010047:Ovalbumin
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