Effects of corticosteroid on the expression of thymus and activation-regulated chemokine in a murine model of allergic asthma.
BACKGROUND
Thymus and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically attracts T-helper (Th) 2 cells positive for the CC chemokine receptor 4 (CCR4(+)). Corticosteroids reduce airway inflammation, as reflected by reduced numbers of eosinophils and T cells and reduced expression of cytokines. We investigated TARC production and the inhibitory effects of corticosteroids on TARC expression in a murine model of allergic asthma.


METHODS
BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) with alum. Once daily for 1 week, mice received injections of dexamethasone or 0.2 ml saline (control), then 1 h later inhaled aerosolized 1% OVA for 30 min. Mice were killed 24 h after OVA challenge for bronchoalveolar lavage and lung tissue examination.


RESULTS
TARC was expressed mainly in the bronchial epithelial cells. Dexamethasone attenuated OVA-induced airway eosinophilia, lymphocyte infiltration, and airway hyperresponsiveness. Dexamethasone also decreased TARC production in the bronchoalveolar lavage fluid and decreased expression of TARC mRNA and TARC protein in lung tissue.


CONCLUSIONS
The corticosteroid dexamethasone inhibits TARC production in a murine model of allergic asthma in vivo. The beneficial effect of corticosteroids in bronchial asthma is due in part to their direct inhibitory effects on TARC production.
Kurokawa
Masatsugu
M
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Kokubu
Fumio
F
Matsukura
Satoshi
S
Kawaguchi
Mio
M
Ieki
Koushi
K
Suzuki
Shintarou
S
Odaka
Miho
M
Watanabe
Shin
S
Takeuchi
Hiroko
H
Akabane
Tomoko
T
Asano
Kazuhito
K
Iwase
Michiko
M
Honma
Ikuo
I
Adachi
Mitsuru
M
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000305:Adrenal Cortex Hormones; C499538:Ccl17 protein, mouse; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; C515188:Cxcr3 protein, mouse; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D016210:Methacholine Chloride; D012313:RNA; D003907:Dexamethasone; D010047:Ovalbumin