Alteration of airway hyperresponsiveness and expression of MMP-9 and TIMP-1 in bronchial tissue by nebulized IFN-gamma in murine model of asthma.
- Author:
Young Mok LEE
1
;
Yang Ki KIM
;
Jong Kun PARK
;
Jon SUH
;
Ki Up KIM
;
Do Jin KIM
;
Soo Taek UH
;
Yong Hoon KIM
;
Choon Sik PARK
Author Information
1. Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soon Chun Hyang University, School of Medicine, Seoul, Korea. uhs@hosp.sch.ac.kr
- Publication Type:Original Article
- Keywords:
Bronchial asthma;
IFN-gamma;
MMP-9;
TIMP-1
- MeSH:
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
- From:Journal of Asthma, Allergy and Clinical Immunology
2003;23(4):788-799
- CountryRepublic of Korea
- Language:Korean
-
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.
