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Nonsteroidal antiinflammatories are known to suppress incidence and progression of malignancies including colorectal cancers. However, the precise mechanism of this action remains unknown. Using prostaglandin (PG) receptor knockout mice, we have evaluated a role of PGs in tumor-associated angiogenesis and tumor growth, and identified PG receptors involved.(More)
High fat intake is associated with fat mass gain through fatty acid activation of peroxisome proliferator-activated receptors delta and gamma, which promote adipogenesis. We show herein that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated, and omega-3 polyunsaturated fatty acids, arachidonic acid (C20:4,(More)
We used mice deficient in each of the eight types and subtypes of prostanoid receptors and examined the roles of prostanoids in dextran sodium sulfate-induced (DSS-induced) colitis. Among the prostanoid receptor-deficient mice, only EP4-deficient mice and not mice deficient in either DP, EP1, EP2, EP3, FP, IP, or TP developed severe colitis with 3% DSS(More)
Physical interaction of T cells and dendritic cells (DCs) is essential for T cell proliferation and differentiation, but it has been unclear how this interaction is regulated physiologically. Here we show that DCs produce thromboxane A2 (TXA2), whereas naive T cells express the thromboxane receptor (TP). In vitro, a TP agonist enhances random cell movement(More)
Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1-4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the(More)
TNF-alpha is a critical mediator of hepatic microcirculatory dysfunction during endotoxemia. The present study was to investigate the role of thromboxane A2 (TXA2) and the biological significance of thromboxane prostanoid (TP) receptor signaling in TNF-alpha-mediated hepatic microcirculatory dysfunction in male C57Bl/6 mice. The number of leukocytes(More)
Although thromboxanes (TXs), whose synthesis is regulated by cyclooxygenase (COX), have been suggested to promote inflammation in the liver, little is known about the role of TXA(2) in leukocyte endothelial interaction during endotoxemia. The present study was conducted to investigate the role of TXA(2) as well as that of COX in lipopolysaccharide(More)
Cyclooxygenase (COX)-2 is known to correlate with poor cancer prognosis and to contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal prostaglandin E(2) (PGE(2))-prostaglandin E2 receptor (EP)3 signaling appears critical for tumor-associated angiogenesis and tumor(More)
Agonists for EP4 receptor, a prostaglandin E2 receptor subtype, appear to be a promising therapeutic strategy for ulcerative colitis (UC) due to their anti-inflammatory and epithelial regeneration activities. However, the clinical development of orally-available EP4 agonists for mild to moderate UC has not yet been reported. Furthermore, the possibility of(More)