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

Abstract

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.

TSG-6 Protein Is Crucial for the Development of Pulmonary Hyaluronan Deposition, Eosinophilia, and Airway Hyperresponsiveness in a Murine Model of Asthma

“…Interestingly, PGD 2 and its high affinity receptors DP1 and CRTH2 (chemoattractant-homologous receptor expressed on Th2 cells) have been shown to be crucial for the promotion and maintenance of allergic responses (51)(52)(53)(54)(55). Importantly, although PGD 2 promotes inflammatory responses through its CRTH2 receptor, which is selectively expressed on eosinophils, Th2 T cells, and basophils (54,55), PGD 2 also has anti-inflammatory and inhibitory effects on neutrophils (56,57). Therefore, it is possible that TSG-6 contributes to the induction of robust allergic inflammation and AHR through promoting the production of PGD 2 .…”

Prostaglandin D2Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

“…Prostaglandin D 2 (PGD 2 ) is a well known inflammatory mediator in peripheral tissues (Matsuoka et al, 2000;Honda et al, 2003;Kabashima and Narumiya, 2003), invoking airway inflammation (Matsuoka et al, 2000;Shiraishi et al, 2005), inhibiting platelet aggregation (Yun et al, 1991), and causing peripheral vasodilatation (Soter et al, 1983;Alving et al, 1991). PGD 2 is synthesized by hematopoietic PGD synthase (HPGDS) and lipocalin-type PGDS (L-PGDS) and exerts its actions by binding to specific receptors, DP 1 or DP 2 (Kabashima and Narumiya, 2003;Nagata and Hirai, 2003).…”

Cyclooxygenase-2/Prostaglandin D2/CRTH2 Pathway Mediates Double-Stranded RNA-Induced Enhancement of Allergic Airway Inflammation

“…We have reported that COX-2 inhibitors, which stop the synthesis of PGD 2 in the lungs of allergen-sensitized and exposed guinea pigs, attenuated the accumulation of eosinophil in the airways (19). Others have reported that the overexpression of PGD synthase or inhalation of aerosolized PGD 2 enhanced the allergen-induced airway eosinophilia in mice (20,21).…”