Role of metallothionein in antigen-related airway inflammation.
Metallothionein (MT) is a protein that can be induced by inflammatory mediators and participates in cytoprotection. However, its role in antigen-related inflammation remains to be established. We determined whether intrinsic MT protects against antigen-related airway inflammation induced by ovalbumin (OVA) in MT-I/II null (MT [-/-]) mice and in corresponding wild-type (WT) mice. MT (-/-) mice and WT mice were intratracheally challenged with OVA (1 mug per body) biweekly four times. Twenty-four hours after the last OVA challenge, significant increases were shown in the numbers of total cells, eosinophils, and neutrophils in bronchoalveolar lavage fluid from MT (-/-) mice than in those from WT mice. The protein level of interleukin-1beta (IL-1beta) was significantly greater in MT (-/-) mice than in WT mice after OVA challenge. Immunohistochemical analysis showed that the formations of 8-oxy-deoxyguanosine and nitrotyrosine in the lung were more intense in MT (-/-) mice than in WT mice after OVA challenge. These results indicate that endogenous MT is a protective molecule against antigen-related airway inflammation induced by OVA, at least partly, via the suppression of enhanced lung expression of IL-1beta and via the antioxidative properties. Our findings suggest that MT may be a therapeutic target for the treatment of antigen-related airway inflammatory diseases such as bronchial asthma.
Inoue
Ken-Ichiro
K
Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Sakurai
Miho
M
Ichinose
Takamichi
T
Sadakane
Kaori
K
Hiyoshi
Kyoko
K
Sato
Masahiko
M
Shimada
Akinori
A
Inoue
Mamoru
M
Yoshikawa
Toshikazu
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001991:Bronchitis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D007150:Immunohistochemistry; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D051379:Mice; D014132:Trachea / Q000276:immunology / Q000503:physiopathology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000941:Antigens; D018925:Chemokines; D016207:Cytokines; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008668:Metallothionein; D003849:Deoxyguanosine