Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse.
Tenascin C (TN-C) is an extracellular matrix glycoprotein whose expression is increased in several inflammatory diseases of the lung, including bronchial asthma. However, the exact function of TN-C in the pathogenesis of lung inflammation remains unclear. In the present study, we compared the degree of bronchial asthma in wild-type and TN-C-deficient (-/-) BALB/c mice. Bronchial asthma was induced by sensitization and challenge with ovalbumin. Littermates treated with saline were used as controls. Cytokines in bronchoalveolar lavage fluid and plasma were measured by enzyme immunoassays. The number of eosinophils in the lung was significantly increased in wild-type mice compared with TN-C-knockout mice. Airway hyperreactivity, NF-kappaB activation and concentrations of monocyte chemoattractant protein-1, IL-5, IL-13, metalloproteinase-9 and immunoglobulin-E in the bronchoalveolar lavage fluid were significantly decreased in ovalbumin-sensitized/challenged TN-C-knockout mice compared with their wild-type counterparts. In vitro experiments disclosed that TN-C significantly stimulates the secretion of IL-5, IL-13, IFN-gamma and immunoglobulin-E from spleen lymphocytes. These observations suggest that TN-C is involved in the pathogenesis of bronchial asthma.
Nakahara
Hiroki
H
Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu-city, Japan.
Gabazza
Esteban C
EC
Fujimoto
Hajime
H
Nishii
Yoichi
Y
D'Alessandro-Gabazza
Corina N
CN
Bruno
Nelson E
NE
Takagi
Takehiro
T
Hayashi
Tatsuya
T
Maruyama
Junko
J
Maruyama
Kazuo
K
Imanaka-Yoshida
Kyoko
K
Suzuki
Koji
K
Yoshida
Toshimichi
T
Adachi
Yukihiko
Y
Taguchi
Osamu
O
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019063:Tenascin / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018418:Th2 Cells / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; D019063:Tenascin; D010047:Ovalbumin