The PPARγ ligand, rosiglitazone, reduces airways hyperresponsiveness in a murine model of allergen-induced inflammation

Autor: Darren J. Fernandes, Jane E. Ward, Lilly Quan, C.C. Taylor, John V Bonacci, Alastair G. Stewart
Rok vydání: 2006
Předmět:
Time Factors
Vasodilator Agents
Peroxisome proliferator-activated receptor
Ligands
Bronchoconstrictor Agents
Mice
Pharmacology (medical)
Receptor
Methacholine Chloride
chemistry.chemical_classification
biology
medicine.diagnostic_test
respiratory system
Trachea
medicine.anatomical_structure
Matrix Metalloproteinase 2
Female
Goblet Cells
medicine.symptom
Cell activation
Bronchoalveolar Lavage Fluid
Injections
Intraperitoneal
Muscle Contraction
medicine.drug
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Ovalbumin
Guinea Pigs
Inflammation
In Vitro Techniques
Rosiglitazone
Internal medicine
Respiratory Hypersensitivity
medicine
Animals
Goblet cell
Hyperplasia
Dose-Response Relationship
Drug
business.industry
Biochemistry (medical)
Pneumonia
Allergens
Mice
Inbred C57BL
PPAR gamma
Disease Models
Animal
Bronchoalveolar lavage
Endocrinology
chemistry
biology.protein
Thiazolidinediones
Methacholine
business
Zdroj: Pulmonary Pharmacology & Therapeutics. 19:39-46
ISSN: 1094-5539
DOI: 10.1016/j.pupt.2005.02.005
Popis: There is considerable interest in the role of peroxisome proliferator activated receptors (PPARs) as ligand-activated transcription factors in the airways. This study examines the effects of a potent synthetic PPARgamma ligand, rosiglitazone (RG), in a murine model of allergen-induced inflammation, to explore its potential regulation of airways inflammation, structure and function. C57BL/6 mice were sensitised with ovalbumin (OVA, 50 microg i.p., days 0, 12) and challenged with aerosolized OVA (1% w v(-1), 30 min day(-1)) for 7 days (days 20-26). Mice were treated with RG (5 mg kg(-1) i.p.) or vehicle during the challenge period. The OVA challenge induced increases in leukocyte number and MMP-2 activity in bronchoalveolar lavage fluid and in goblet cell number in lung tissue obtained on Day 27. RG failed to inhibit inflammatory cell infiltration, MMP-2 activity or goblet cell hyperplasia. Respiratory resistance in response to methacholine (MCh i.v.) was greater in OVA-challenged mice than saline-challenged mice and this airways hyperresponsiveness (AHR) was reduced by RG. However, RG did not affect MCh-induced contraction in isolated guinea-pig tracheal rings, nor did it influence the airway obstruction induced by MCh in saline-challenged mice, so a direct effect on airway obstruction is unlikely. These data suggest that RG modulates AHR in this model, by a mechanism that is also potentially independent of an anti-inflammatory action.
Databáze: OpenAIRE
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