Impaired induction of allergic lung inflammation byAlternaria alternatamutant MAPK homologue Fus3
| Autor: | Naseem Khorram, Siwy Ling Yang, Sean Lund, Taylor A. Doherty, Rachel Baum, Kuang-Ren Chung, Hee-Kyoo Kim |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
Allergy Ovalbumin Genes Fungal Clinical Biochemistry Inflammation medicine.disease_cause Alternaria alternata Article Microbiology Fungal Proteins Mice Th2 Cells Allergen otorhinolaryngologic diseases medicine Animals Humans Eosinophilia Lung Molecular Biology Sensitization Mitogen-Activated Protein Kinase Kinases biology Alternaria Allergens respiratory system biology.organism_classification medicine.disease Asthma Immunity Innate respiratory tract diseases Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Mutation Immunology biology.protein Female medicine.symptom |
| Zdroj: | Experimental Lung Research. 39:399-409 |
| ISSN: | 1521-0499 0190-2148 |
| DOI: | 10.3109/01902148.2013.835009 |
| Popis: | The fungal allergen Alternaria alternata is associated with development of asthma, though the mechanisms underlying the allergenicity of Alternaria are largely unknown. The aim of this study was to identify whether the MAP kinase homologue Fus3 of Alternaria contributed to allergic airway responses. Wild-type (WT) and Fus3 deficient Alternaria extracts were given intranasal to mice. Extracts from Fus3 deficient Alternaria that had a functional copy of Fus3 introduced were also administered (CpFus3). Mice were challenged once and levels of BAL eosinophils and innate cytokines IL-33, thymic stromal lymphopoeitin (TSLP), and IL-25 (IL-17E) were assessed. Alternaria extracts or protease-inhibited extract were administered with (OVA) during sensitization prior to ovalbumin only challenges to determine extract adjuvant activity. Levels of BAL inflammatory cells, Th2 cytokines, and OX40-expressing Th2 cells as well as airway infiltration and mucus production were measured. WT Alternaria induced innate airway eosinophilia within 3 days. Mice given Fus3 deficient Alternaria were significantly impaired in developing airway eosinophilia that was largely restored by CpFus3. Further, BAL IL-33, TSLP, and Eotaxin-1 levels were reduced after challenge with Fus3 mutant extract compared with WT and CpFus3 extracts. WT and CpFus3 extracts demonstrated strong adjuvant activity in vivo as levels of BAL eosinophils, Th2 cytokines, and OX40-expressing Th2 cells as well as peribronchial inflammation and mucus production were induced. In contrast, the adjuvant activity of Fus3 extract or protease-inhibited WT extract was largely impaired. Finally, protease activity and Alt a1 levels were reduced in Fus3 mutant extract. Thus, Fus3 contributes to the Th2-sensitizing properties of Alternaria. |
| Databáze: | OpenAIRE |
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