J Asthma Allergy Clin Immunol.  2003 Dec;23(4):788-799.

Alteration of airway hyperresponsiveness and expression of MMP-9 and TIMP-1 in bronchial tissue by nebulized IFN-gamma in murine model of asthma

• Lee YM
• Kim YK
• Park JK
• Suh J
• Kim KU
• Kim DJ
• Uh ST
• Kim YH
• Park CS

Abstract

BACKGROUND
A bronchial asthma is characterized with airway inflammation, tissue damage, and deposition of extracellular matrix protein, which may be mediated, in part, through released matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Recent studies suggest that interferon-gamma (IFN-gamma) may attenuate the inflammation of bronchial asthma.
OBJECTIVES
To investigate the effects of rIFN-gamma administered by ultrasonic nebulization through the airway on airway hyperresponsiveness and expression of MMP-9 and TIMP-1 in murine model of asthma. METHODS: Six-week-old female BALB/c mice were sensitized by means of intraperitoneal injection of ovalbumin (OVA) or saline, and then exposed to aerosolized OVA or saline. The rIFN-gamma treatment group pretreated with inhalation of aerosolized rIFN-gamma 1 day before OVA or saline inhalation. Twenty-four hour later after last challenge, the airway hyperreactivity was measured by placing mice in a barometric plethysmography. Bronchoalveolar lavage (BAL) fluids, peripheral blood, and lung tissue were obtained from individual mouse twenty-four hours after measurement of airway hyperreactivity. RESULTS: The administration of aerosolized IFN-gamma decreased OVA induced eosinophil recruitment in BAL fluid, specific IgE to OVA, airway hyperresponsiveness, and MMP-9 expression on bronchial tissue. The active MMP-9 was not observed in IFN-gamma pretreated-group in contrast to OVA-group in gelatin zymography of BAL fluids. CONCLUSION: Our study indicates that aerosolized IFN-gamma prevents pathophysiologic alterations of bronchial asthma including expression of MMP-9, and therefore IFN-gamma may be a good therapeutic strategy in clinical practice.

Keyword

Bronchial asthma; IFN-gamma; MMP-9; TIMP-1

MeSH Terms

Animals
Asthma*
Bronchoalveolar Lavage
Eosinophils
Extracellular Matrix
Female
Gelatin
Humans
Immunoglobulin E
Inflammation
Inhalation
Injections, Intraperitoneal
Interferon-gamma
Lung
Matrix Metalloproteinase 9
Mice
Ovalbumin
Ovum
Plethysmography
Tissue Inhibitor of Metalloproteinase-1*
Ultrasonics
Gelatin
Immunoglobulin E
Interferon-gamma
Matrix Metalloproteinase 9
Ovalbumin
Tissue Inhibitor of Metalloproteinase-1