RRC ID 42029
Author Yuda H, Adachi Y, Taguchi O, Gabazza EC, Hataji O, Fujimoto H, Tamaki S, Nishikubo K, Fukudome K, D'Alessandro-Gabazza CN, Maruyama J, Izumizaki M, Iwase M, Homma I, Inoue R, Kamada H, Hayashi T, Kasper M, Lambrecht BN, Barnes PJ, Suzuki K.
Title Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.
Journal Blood
Abstract Asthma is one of the most common diseases and is characterized by airway obstruction, airway inflammation, and increased airway responsiveness. Glucocorticoids are very effective in treatment, but their long-term use is associated with several side effects, so that new anti-inflammatory drugs are in development. Activated protein C (APC) is a serine protease with potent anti-inflammatory effects. This study evaluated the effect of inhaled APC on airway inflammation and hyperresponsiveness in a murine asthma model. Asthma was induced in BALB/c mice by exposure to chicken egg ovalbumin (OVA), and the effect of inhaled APC was assessed by administering prior to OVA exposure. Inhalation of APC significantly inhibited the expression of T helper 2 (Th2) cytokines, immunoglobulin E (IgE), eosinophilic inflammation, and hyperresponsiveness. APC also significantly suppressed the expression of Th2 cytokines and IgE from lymphocytes isolated from OVA-sensitized/challenged animals. In addition, binding of signal transducer and activator of transcription 6 (STAT6) and nuclear factor kappa B (NF-kappa B) oligonucleotides to lung nuclear proteins was significantly reduced in mice treated with inhaled APC. In brief, the exogenous supplementation of APC inhibits the immunologic and inflammatory responses induced by Th2 cytokines in a mouse model of asthma and may represent a novel anti-inflammatory treatment.
Volume 103(6)
Pages 2196-204
Published 2004-3-15
DOI 10.1182/blood-2003-06-1980
PII S0006-4971(20)50014-1
PMID 14604971
MeSH Animals Antibodies Antigens, CD Asthma / drug therapy* Asthma / immunology Asthma / metabolism Biomarkers Blood Coagulation Factors / immunology Bronchial Hyperreactivity / drug therapy* Bronchial Hyperreactivity / immunology Bronchial Hyperreactivity / metabolism Cytokines / metabolism Dinoprostone / metabolism Disease Models, Animal Dose-Response Relationship, Drug Endothelial Protein C Receptor Endothelins / genetics Endothelins / immunology Eosinophils / immunology Female Glycoproteins HeLa Cells Humans Hypersensitivity / drug therapy Hypersensitivity / immunology Hypersensitivity / metabolism Immunoglobulin E / metabolism Mice Mice, Inbred BALB C NF-kappa B / metabolism Nitric Oxide / metabolism Ovalbumin / immunology Protein C / pharmacology* Receptor, PAR-1 / antagonists & inhibitors Receptors, Cell Surface STAT6 Transcription Factor Specific Pathogen-Free Organisms Th2 Cells / drug effects Th2 Cells / immunology* Thrombin / metabolism Trans-Activators / metabolism U937 Cells
IF 17.794
Times Cited 79
Human and Animal Cells