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Prostaglandin D₂ Reinforces Th2 Type Inflammatory Responses of Airways to Low-dose Antigen through Bronchial Expression of Macrophage-derived Chemokine

Kyoko Honda¹, Masafumi Arima², Gang Cheng¹, Shinsuke Taki³, Hirokuni Hirata¹, Fukiko Eda¹, Fumiya Fukushima¹, Bunpei Yamaguchi¹, Masahiko Hatano², Takeshi Tokuhisa² and Takeshi Fukuda¹

¹ Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan
² Department of Developmental Genetics, Graduate School of Medicine Chiba University, Chiba 260-8670, Japan
³ Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan

Address correspondence to Dr. Takeshi Fukuda, Dept. of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Mibu-machi Shimotsuga-gun, Tochigi 321-0293, Japan. Phone: 81-282-87-2151; Fax: 81-282-86-5080; email: t-fukuda{at}dokkyomed.ac.jp

PGD₂, a lipid mediator released from mast cells, is known to participate in allergic reactions. However, the mechanism by which PGD₂ contributes to such reactions remains unclear. We established a novel experimental model of asthma that permitted direct assessment of the role of PGD₂ in airway inflammation. Antigen-sensitized mice were exposed to aerosolized prostaglandin D₂ (PGD₂) 1 d before challenge with low-dose aerosolized antigen. Not only the numbers of eosinophils, lymphocytes, and macrophages but also the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid were higher in PGD₂-pretreated mice than in control mice. The expression of macrophage-derived chemokine (MDC), a chemoattractant for Th2 cells, was greater in PGD₂-pretreated mice than in control. Injection of anti-MDC antibody into PGD₂-pretreated mice markedly inhibited inflammatory cell infiltration as well as Th2 cyto-kine production after antigen challenge. These results indicate that PGD₂ accelerates Th2 type inflammation by induction of MDC. Our results suggest that this mechanism may play a key role in the development of human asthma and that MDC might be a target molecule for therapeutic intervention.

Key Words: bronchial asthma • chemokines • epithelial cells • prostanoids • Th2 cells

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