Identification and Characterization of a Novel Type of Membrane-Associated Prostaglandin E Synthase

Tanikawa, Naomi; Ohmiya, Yoshihiro; Ohkubo, Hiroaki; Hashimoto, Katsuyuki; Kangawa, Kenji; Kojima, Masami; Ito, Seiji; Watanabe, Kikuko

doi:10.1006/bbrc.2002.6531

Cited by 284 publications

(231 citation statements)

References 21 publications

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“…[35][36][37] Expression of mPGES1 is markedly induced by pro-inflammatory stimulation in various tissues. 35 PGES1 is involved in the COX-2-mediated PGE2-biosynthetic pathway 35 ; mPGES2 is abundant in brain, heart, skeletal muscle, kidney, and liver 37 ; cPGES is distributed ubiquitously in the cytosol of various cells 36 ; and COX-1 contributes to PGE2 generation by PGES2 and cPGES.…”

Section: Discussionmentioning

confidence: 99%

“…PGES is classified into three types, glutathione-dependent membrane-bound PGES (mPGES1), glutathione-independent membrane-bound PGES (mPGES2), and cytosolic PGES (cPGES). [35][36][37] Hpgds transcripts that encode H-PGDS were readily detected in both BMBAs and BMMCs by RT-PCR. In contrast, Ptgds transcripts that encode L-PGDS were only detected in BMMCs ( Figure 5, A and B).…”

Section: Basophils Express H-pgds and Pgesmentioning

confidence: 99%

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FcεRI, but Not FcγR, Signals Induce Prostaglandin D2 and E2 Production from Basophils

Ugajin

Satoh

Kanamori

et al. 2011

The American Journal of Pathology

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Prostaglandin (PG) D2 and PGE2 are arachidonic acid metabolites that are generated though an isomerization reaction catalyzed by PG synthases. PGs have been implicated in immunologic reactions in addition to a wide range of physiological functions. It has long been thought that basophils, in contrast to mast cells, do not synthesize PGs, although they do release leukotrienes and platelet-activating factor. Here, we show that basophils function as a source of PGD2 and PGE2. In vitrocultured basophils from mouse bone marrow produced both PGD2 and PGE2 in response to IgE ؉ antigen (Ag), but not to IgG ؉ Ag. Release of PGs was almost completely abrogated in cultured basophils from FcR␥-chain ؊/؊ mice, indicating the involvement of Fc RI. Basophils freshly isolated from bone marrow cells (primary basophils) were also capable of secreting PGD2 and PGE2. Although the amount of PGD2 released from primary basophils was lower than that from mast cells, the capability of primary basophils to generate PGE2 was more potent than that of mast cells. Transcripts and proteins for both hematopoietic-type PGD synthase and PGE synthase were detected in basophils. In addition, human basophils, like mouse basophils, also produced PGD2 through IgE-mediated stimulation. Thus, basophils could be an important source of PGD2/ PGE2 and may contribute to allergic inflammation and immune responses. Prostaglandins, such as PGD2 and PGE2, are cyclooxygenase (COX) metabolites of arachidonic acids. They have a wide range of biological activities, including relaxation and contraction of smooth muscles, and modulation of neuronal activity. 1 PGD2 is principally produced by activated mast cells and, to a lesser extent, by T helper cell 2 (Th2) cells and dendritic cells 2-4 and exerts its effect through D prostanoid 5 and chemoattractant receptor-homologous molecule receptors expressed onTh2 lymphocytes (CRTH2). 6 A number of recent studies have shown that PGD2 is involved in inflammatory reactions. Mast cell-derived PGD2 suppresses IL-12 production by dendritic cells that induce Th2 responses in vivo. 7 PGD2 both activates and induces chemotaxis of Th2 cells, eosinophils, and basophils. 6 A large amount of PGD2 is detected in broncho-alveolar lavage fluid during allergen-induced airway inflammation. 8 Transgenic mice overexpressing human PGD synthase showed exacerbation of ovalbumin (OVA)-induced lung inflammation associated with pronounced eosinophilia and increased Th2 cytokine production. 9 In our previous studies, mice deficient in the CRTH2 gene were characterized by alleviated IgE-mediated cutaneous responses, contact hypersensitivity reactions, 10 and cedar pollen dermatitis. 11 However, PGE2 is produced by a variety of cells, including fibroblasts and macrophages, and exerts its effects via prostaglandin E2 (EP)1, EP2, EP3, and EP4 receptors. 12 PGE2 acts on T cells to enhance production of Th2-type cytokines and to inhibit production of Th1 cytokines in vitro, 13 whereas another study showed that PGE2 facilitates Th1 differentiation via EP...

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Section: Discussionmentioning

confidence: 99%

Section: Basophils Express H-pgds and Pgesmentioning

confidence: 99%

FcεRI, but Not FcγR, Signals Induce Prostaglandin D2 and E2 Production from Basophils

Ugajin

Satoh

Kanamori

et al. 2011

The American Journal of Pathology

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“…Expression of mPGES1 is highly inducible in states of injury and inflammation, often in parallel with expression of the inducible COX-2 (12,13). More recently, a second putative microsomal PGES (mPGES2) that can also generate PGE 2 from endoperoxides in vitro with high affinity and specificity was identified (14,15), but its capacity to generate PGE 2 in vivo is not clear. A third form of PGES has been isolated from cytoplasmic extracts (16).…”

mentioning

confidence: 99%

Role of Microsomal Prostaglandin E Synthase 1 in the Kidney

François

Facemire

Kumar

et al. 2007

Journal of the American Society of Nephrology

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Prostaglandin E 2 (PGE 2 ) is one of the most ubiquitous prostanoids in the kidney, where it may influence a wide range of physiologic functions. PGE 2 is generated through enzymatic metabolism of prostanoid endoperoxides by specific PGE synthases (PGES). Several putative PGES have been identified and cloned, including the membrane-associated, inducible microsomal PGES1 (mPGES1), which is expressed in the kidney. To evaluate the physiologic role of mPGES1 in the kidney, mice with targeted disruption of mPges1 gene were studied, with a focus on responses where PGE 2 has been implicated, including urinary concentration, regulation of blood pressure, and response to a loop diuretic. The absence of mPGES1 was associated with a 50% decrease in basal excretion of PGE 2 in urine (P < 0.001). In female but not male mPGES1-deficient mice, there was a reciprocal increase in basal excretion of other prostanoids. Nonetheless, urinary osmolalities were similar in mPges1 ؉/؉ and mPges1 ؊/؊ mice at baseline and after 12 h of water deprivation. Likewise, there were no differences in blood pressure between mPGES1-deficient and wild-type mice on control or high-or low-salt diets. The furosemide-induced increase in urinary PGE 2 excretion that was seen in wild-type mice was attenuated in mPGES1-deficient mice. However, furosemide-associated diuresis was reduced only in male, not female, mPGES1-deficient mice. Stimulation of renin by furosemide was not affected by mPGES1 deficiency. These data suggest that mPGES1 contributes to basal synthesis of PGE 2 , but there are other pathways that lead to renal PGE 2 synthesis. Moreover, there are significant gender differences in physiologic contributions of mPGES1 to control kidney function.

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“…3A). Both PTGES2 and PTGES3 are constitutively expressed in various cell types, and utilize PGH 2 produced by both COX-1 and COX-2 as a substrate to produce PGE2 (Murakami et al, 2000;Tanikawa et al, 2002;Murakami et al, 2003). Therefore, down-regulation of PTGES1 gene expression may not be a main reason for the decrease in PGE2 levels during adipocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…3A). There are three prostaglandin E synthase subtypes: prostaglandin E synthase 1 (PTGES1, microsomal prostaglandin E synthase), prostaglandin E synthase 2 (PTGES2), and prostaglandin E synthase 3 (PTGES3, cytosolic prostaglandin E synthase) (Murakami et al, 2000;Tanikawa et al, 2002;Murakami et al, 2003). As shown in Fig.…”

Section: Down-regulation Of Prostaglandin E Synthase 1 May Not Sufficmentioning

confidence: 99%

15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human Bone Marrow Mesenchymal Stem Cells

Noh¹,

Lee²

2010

Biomolecules and Therapeutics

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-Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, PPARγ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, significantly reduced the levels of anti-adipogenic PGE 2 in IDX-conditioned hBM-MSC culture supernatants when compared to PGE2 levels in the absence of PPARγ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease PGE2 levels in culture. These results suggest that the role of PPARγ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic PGE 2 levels through the up-regulation of HPGD expression.

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Identification and Characterization of a Novel Type of Membrane-Associated Prostaglandin E Synthase

Cited by 284 publications

References 21 publications

FcεRI, but Not FcγR, Signals Induce Prostaglandin D2 and E2 Production from Basophils

FcεRI, but Not FcγR, Signals Induce Prostaglandin D2 and E2 Production from Basophils

Role of Microsomal Prostaglandin E Synthase 1 in the Kidney

15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human Bone Marrow Mesenchymal Stem Cells

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