Effects of corticosteroids on osteopontin expression in a murine model of allergic asthma.
BACKGROUND
Osteopontin (OPN) contributes to the development of T helper 1 (Th1)-mediated immunity and Th1-associated diseases. However, the role of OPN in bronchial asthma is unclear. Corticosteroids reduce airway inflammation, as reflected by the low eosinophil and T-cell counts, and the low level of cytokine expression. We investigated OPN production and the inhibitory effects of corticosteroids on OPN production in a murine model of allergic asthma.


METHODS
BALB/c mice were sensitized by intraperitoneal injections of ovalbumin (OVA) with alum. Some mice received daily injections of dexamethasone (DEX) or phosphate-buffered saline for 1 week. All OVA-challenged mice were exposed to aerosolized 1% OVA for 30 min an hour after these injections. After the OVA challenge, the mice were killed, and bronchoalveolar lavage (BAL) fluid and lung tissue were examined.


RESULTS
The levels of OPN protein in BAL fluid and OPN mRNA in lung tissue increased after OVA challenge. Most OPN-expressing cells were CD11c+ cells and some were T cells. DEX decreased the levels of OPN protein in the BAL fluid, and those of OPN mRNA and OPN protein in lung tissue.


CONCLUSIONS
OPN may play an important role in allergic bronchial asthma. Corticosteroids inhibit OPN production in mice with allergic asthma. The beneficial effect of corticosteroids in bronchial asthma is partly due to their inhibitory effects on OPN production.
Kurokawa
Masatsugu
M
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. cdl94140@par.odn.ne.jp
Konno
Satoshi
S
Matsukura
Satoshi
S
Kawaguchi
Mio
M
Ieki
Koushi
K
Suzuki
Shintarou
S
Odaka
Miho
M
Watanabe
Shin
S
Homma
Tetsuya
T
Sato
Masayuki
M
Takeuchi
Hiroko
H
Hirose
Takashi
T
Huang
Shau-Ku
SK
Adachi
Mitsuru
M
D000818:Animals; D001249:Asthma / Q000276:immunology*; D018845:CD11 Antigens / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007114:Immunization; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology
D018845:CD11 Antigens; D015704:CD4 Antigens; D005938:Glucocorticoids; D012333:RNA, Messenger; D053495:Osteopontin; D003907:Dexamethasone; D010047:Ovalbumin