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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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
Substances
-
Antibodies
-
Antigens, CD
-
Biomarkers
-
Blood Coagulation Factors
-
Cytokines
-
Endothelial Protein C Receptor
-
Endothelins
-
Glycoproteins
-
NF-kappa B
-
PROCR protein, human
-
Protein C
-
Receptor, PAR-1
-
Receptors, Cell Surface
-
STAT6 Transcription Factor
-
STAT6 protein, human
-
Stat6 protein, mouse
-
Trans-Activators
-
leukocyte procoagulant activity
-
Nitric Oxide
-
Immunoglobulin E
-
Ovalbumin
-
Thrombin
-
Dinoprostone