Molecular Characterization of Trimellitic Anhydride–induced Respiratory Allergy in Brown Norway Rats

Autor: Joost P. Bruijntjes, André Boorsma, Hans Muijser, Kitty C.M. Verhoeckx, Josje H.E. Arts, Rob H. Stierum, Marijana Radonjic, Marinus Dansen, Wilbert H. M. Heijne, C. Frieke Kuper
Přispěvatelé: TNO Kwaliteit van Leven
Rok vydání: 2008
Předmět:
Proteomics
Allergy
Signal transduction
Toxicology
Immunoglobulin E
Toll like receptor
Bronchoalveolar Lavage
Trimellitic anhydride
chemistry.chemical_compound
Rats
Inbred BN
Pathology
Cluster Analysis
Analysis of variance
Respiratory system
Phthalic anhydride
Lung
Lung lavage
Oligonucleotide Array Sequence Analysis
Principal Component Analysis
biology
medicine.diagnostic_test
Allergen
Toll-Like Receptors
Respiratory tract allergy
respiratory system
Immunohistochemistry
Blood
Nonparametric test
medicine.anatomical_structure
Female
medicine.symptom
Signal Transduction
Principal component analysis
Inflammation
Brown Norway rat
Article
Statistics
Nonparametric
Pathology and Forensic Medicine
Cluster analysis
Genetics
Respiratory Hypersensitivity
medicine
Animals
Biology
Molecular Biology
Analysis of Variance
Animal
Gene Expression Profiling
DNA microarray
Cell Biology
Allergens
medicine.disease
Rats
respiratory tract diseases
Drug effect
Gene expression profiling
Metabolism
Bronchoalveolar lavage
chemistry
Toxicology and Applied Pharmacology
Phthalic Anhydrides
Immunology
biology.protein
Rat
Zdroj: Toxicologic pathology, 7, 36, 985-998
ISSN: 1533-1601
0192-6233
DOI: 10.1177/0192623308327410
Popis: To contribute to the hazard identification of low molecular weight (LMW) respiratory allergens, respiratory allergy induced by trimellitic anhydride (TMA) was characterized by whole genome analysis of lung tissue and blood proteomics in Brown Norway rats. Dermal sensitization (50% and 25% w/v) with TMA and an inhalation challenge of 15 mg/m3 TMA-induced apneas, laryngeal inflammation, increased numbers of eosinophils, neutrophils and macrophages in bronchoalveolar lavage (BAL), and increased immunoglobulin E levels in serum and lung tissue. Whole genome analysis of lung, sampled 24 hours after challenge, showed expression changes of not only genes belonging to several Gene Ontology groups with up-regulation of inflammatory-associated genes and those associated with lung remodeling but also genes involved in downsizing these processes. Blood proteomics reflected activation of inflammation-inhibiting pathways. Unsensitized animals challenged with TMA exhibited also an increased number of macrophages in BAL, but gene expression in the above-mentioned gene pathways was unchanged or down-regulated. The authors conclude that parameters for lung remodeling can be a valuable tool in hazard identification of LMW respiratory allergens.
Databáze: OpenAIRE
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