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Stat6-Deficient Mice Develop Airway Hyperresponsiveness and Peribronchial Fibrosis during Chronic Fungal Asthma
- Source :
- The American Journal of Pathology. 160:481-490
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- Signal transducer and activator of transcription 6 (Stat6) is critical for Th2-mediated responses during allergic airway disease. To investigate the role of Stat6 in fungus-induced airway hyperresponsiveness and remodeling, Stat6-deficient (Stat6−/−) and Stat6-wildtype (Stat6+/+) mice were sensitized to Aspergillus fumigatus and airway disease was subsequently assessed in both groups at days 21, 30, 38, and 44 after an intratracheal challenge with live A. fumigatus conidia. At all times after conidia, histological analysis revealed an absence of goblet cell hyperplasia and markedly diminished peribronchial inflammation in Stat6−/− mice in contrast to Stat6+/+ mice. Airway hyperresponsiveness and peribronchial fibrosis in Stat6−/− mice were significantly reduced at day 21 after conidia compared with Stat6+/+ mice, but both groups exhibited significant, similar increases in these parameters at all subsequent times after conidia. In separate experiments, IL-13-responsive cells in Stat6−/− mice were targeted via the daily intranasal administration of 200 ng of IL-13-PE38QQR (IL13-PE), comprised of human IL-13 and a derivative of Pseudomonas exotoxin, from days 38 to 44 after the conidia challenge. IL13-PE treatment abolished airway hyperresponsiveness, but not peribronchial fibrosis in Stat6−/− mice. Taken together, these data demonstrate that the chronic development of airway hyperresponsiveness during fungal asthma is IL-13-dependent but Stat6-independent.
- Subjects :
- Chemokine CCL11
Pulmonary Fibrosis
T-Lymphocytes
Mice, Transgenic
Immunoglobulin E
Pathology and Forensic Medicine
Aspergillus fumigatus
Mice
Transforming Growth Factor beta
Fibrosis
parasitic diseases
Pulmonary fibrosis
Leukocytes
medicine
Animals
Humans
Chemokine CCL5
Lung
Chemokine CCL2
Interleukin 4
STAT6
Mice, Inbred BALB C
Interleukin-13
integumentary system
biology
Aspergillosis, Allergic Bronchopulmonary
respiratory system
biology.organism_classification
medicine.disease
Asthma
medicine.anatomical_structure
Chemokines, CC
Chronic Disease
Immunology
Interleukin 13
Trans-Activators
biology.protein
Collagen
Interleukin-4
Bronchial Hyperreactivity
STAT6 Transcription Factor
Bronchoalveolar Lavage Fluid
Regular Articles
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 160
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....df01dd7110b20b42a2aef369ecef5145