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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Activating Transcription Factor 3 / genetics
-
Activating Transcription Factor 3 / immunology*
-
Allergens / immunology
-
Animals
-
Asthma / immunology*
-
Bronchial Hyperreactivity / immunology*
-
Bronchoalveolar Lavage Fluid
-
CD4-Positive T-Lymphocytes / immunology
-
Chemokines / genetics
-
Chemokines / immunology
-
Gene Expression Regulation
-
Humans
-
Interleukin-13 / genetics
-
Interleukin-13 / immunology
-
Interleukin-4 / genetics
-
Interleukin-4 / immunology
-
Interleukin-5 / genetics
-
Interleukin-5 / immunology
-
Lung / cytology
-
Lung / immunology
-
Lung / pathology
-
Mice
-
Mice, Knockout
-
Ovalbumin / immunology
-
Pneumonia / immunology*
-
Pneumonia / pathology
-
Promoter Regions, Genetic
-
Pulmonary Eosinophilia / immunology
-
Th2 Cells / immunology
Substances
-
Activating Transcription Factor 3
-
Allergens
-
Chemokines
-
Interleukin-13
-
Interleukin-5
-
Interleukin-4
-
Ovalbumin