Prostaglandin D2 formation and characterization of its synthetases in various tissues of adult rats

Ujihara, Mayumi; Urade, Yoshihiro; Eguchi, Naomi; Hayashi, Hideya; Ikai, Kouichi; Hayaishi, Osamu

doi:10.1016/0003-9861(88)90477-8

Cited by 157 publications

(82 citation statements)

References 35 publications

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“…PGD 2 induces an unusual phenotype on immature DC, modulates their maturation program and favors the differentiation of Th2 cells. Since micromolar concentrations of PGD 2 are detected in certain noninflamed tissues [42] such as the spleen and the bone marrow, it may be the case that PGD 2 modulates DC functions under steady-state conditions. Moreover, the enhanced production of PGD 2 in peripheral sites during inflammation, particularly during the allergic reaction [32] or tumor formation [43], highlights its role on DC functions in pathological conditions and suggests that PGD 2 may be an important component in the control of the immune response in these diseases.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin D₂ affects the differentiation and functions of human dendritic cells: impact on the T cell response

et al. 2005

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The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D 2 (PGD 2 ), a major prostanoid produced during inflammatory reactions, is involved in the control of immune responses, its effect on the differentiation and functions of human monocytederived dendritic cells (MDDC) was studied. We show that DC differentiated in the presence of PGD 2 (PG/DC) have an unusual phenotype, with modifications in the expression of molecules involved in antigen (Ag) capture and presentation, leading to higher endocytic and Ag-processing activities. However, under conditions that necessitated Ag processing and presentation, PG/DC have an impaired ability to stimulate naive T cells, whereas superAg-pulsed DC efficiently promote their proliferation. Upon lipopolysaccharide or TNF-a/IL-1b stimulation, PG/DC phenotypically mature but produce abnormal amounts of immunoregulatory cytokines (decreased IL-12p70/IL-10 ratio). Moreover, mature PG/DC fail to up-regulate the chemokine receptor CCR7 and show an impaired migration towards its ligand CCL19. Finally, PG/DC favor the differentiation of naive T cells toward Th2 cells, an effect dependent on IL-10 and inducible costimulator ligand expression by DC. Most of the herein described effects of PGD 2 on MDDC can be reproduced, usually with a higher efficacy, with a selective D prostanoid receptor (DP)1, but not DP2, agonist. Taken as a whole, these results demonstrate that PGD 2 impacts DC differentiation and functions, and extend the concept that it exerts important roles in immunity.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin D₂ affects the differentiation and functions of human dendritic cells: impact on the T cell response

et al. 2005

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“…Hence, it seems possible that concentrations of PGs sufficient to induce lymphocyte apoptosis can be reached in the local microenvironment, i.e., inflamed tissues, due to the rapid conversion of PGD 2 into its cyclopentenone derivatives (1). The highest expression levels of PGD 2 were detected in bone marrow, spleen, and intestine (63), which constitute the scenario for lymphocyte ontogeny and homeostasis. In this context, it was suggested that the main endogenous producer of PGD 2 may be APCs like dendritic cells, Langerhans cells, monocytes/macrophages, and Kupffer cells (64), although this observation still needs further confirmation.…”

Section: Discussionmentioning

confidence: 99%

Cyclopentenone Prostaglandins Induce Lymphocyte Apoptosis by Activating the Mitochondrial Apoptosis Pathway Independent of External Death Receptor Signaling

Nencioni

Lauber

Grünebach³

et al. 2003

The Journal of Immunology

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15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2) is a naturally occurring cyclopentenone metabolite of PGD2 that possesses both peroxisome proliferator-activated receptor γ (PPAR-γ)-dependent and PPAR-γ-independent anti-inflammatory properties. Recent studies suggest that cyclopentenone PGs may play a role in the down-regulation of inflammation-induced immune responses. In this study, we report that 15d-PGJ2 as well as synthetic PPAR-γ agonists inhibit lymphocyte proliferation. However, only 15d-PGJ2, but not the specific PPAR-γ activators, induce lymphocyte apoptosis. We found that blocking of the death receptor pathway in Fas-associated death domain−/− or caspase-8−/− Jurkat T cells has no effect on apoptosis induction by 15d-PGJ2. Conversely, overexpression of Bcl-2 or Bcl-xL completely inhibits the initiation of apoptosis, indicating that 15d-PGJ2-mediated apoptosis involves activation of the mitochondrial pathway. In line with these results, 15d-PGJ2 induces mitochondria disassemblage as demonstrated by dissipation of mitochondrial transmembrane potential (Δψm) and cytochrome c release. Both of these events are partially inhibited by the broad spectrum caspase inhibitor benzyloxycarbonil-Val-Ala-Asp-fluoromethylketone, suggesting that caspase activation may amplify the mitochondrial alterations initiated by 15d-PGJ2. We also demonstrate that 15d-PGJ2 potently stimulates reactive oxygen species production in Jurkat T cells, and Δψm loss induced by 15d-PGJ2 is prevented by the reactive oxygen species scavenger N-acetyl-l-cysteine. In conclusion, our data indicate that cyclopentenone PGs like 15d-PGJ2 may modulate immune responses even independent of PPAR-γ by activating the mitochondrial apoptosis pathway in lymphocytes in the absence of external death receptor signaling.

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“…The amount of PGE 2 in mouse ears at 0, 1, 2, 3, and 4 days after application of 20 l of 0.5% DMBA was determined by enzyme immunoassay, as described previously (23). In brief, both ears of each mouse were cut off and immediately dropped into liquid nitrogen.…”

Section: Determination Of Pge 2 In Mouse Skinmentioning

confidence: 99%

Carcinogen-Induced Inflammation and Immunosuppression Are Enhanced in Xeroderma Pigmentosum Group A Model Mice Associated with Hyperproduction of Prostaglandin E2

Miyauchi-Hashimoto

Kuwamoto

Urade³

et al. 2001

The Journal of Immunology

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Xeroderma pigmentosum group A (XPA) gene-deficient mice easily developed skin cancers by the application of topical chemical carcinogens as well as by UV irradiation. As certain chemical carcinogens have been shown to be immunosuppressive, we examined the inflammatory and immunosuppressive effects of dimethylbenz(a)anthracene (DMBA) on XPA mice. Compared with wild-type mice, XPA mice showed greater ear swelling and reduction of epidermal Langerhans cells after DMBA application. Topical application of DMBA impaired the induction of contact hypersensitivity, initiated either locally or at distant sites. These DMBA-induced local and systemic immunosuppressions were more greatly enhanced in XPA mice than in wild-type mice. DMBA application induced pronounced production of PGE2, IL-10, and TNF-α in the skin of XPA mice. Treatment with indomethacin, a potent inhibitor of PG biosynthesis, inhibited DMBA-induced inflammation and local immunosuppression. In XPA mice, increased serum IL-10 was detected after DMBA treatment. Excess production of PGE2, TNF-α, and IL-10 after DMBA application may be involved in the enhanced local and systemic immunosuppression in DMBA-treated XPA mice. Susceptibility to DMBA-induced skin tumors in XPA mice may be due to easy impairment of the immune system by DMBA in addition to a defect in the repair of DMBA-DNA adduct. Enhanced immunosuppression by chemical carcinogens as well as the mutagenicity of these mutagens might be associated with the high incidence of internal malignancies seen in XP patients. Moreover, these results supported the hypothesis that persistent DNA damage is a trigger for the production of immunoregulatory cytokines.

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Prostaglandin D2 formation and characterization of its synthetases in various tissues of adult rats

Cited by 157 publications

References 35 publications

Prostaglandin D₂ affects the differentiation and functions of human dendritic cells: impact on the T cell response

Prostaglandin D₂ affects the differentiation and functions of human dendritic cells: impact on the T cell response

Cyclopentenone Prostaglandins Induce Lymphocyte Apoptosis by Activating the Mitochondrial Apoptosis Pathway Independent of External Death Receptor Signaling

Carcinogen-Induced Inflammation and Immunosuppression Are Enhanced in Xeroderma Pigmentosum Group A Model Mice Associated with Hyperproduction of Prostaglandin E2

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Prostaglandin D2 formation and characterization of its synthetases in various tissues of adult rats

Cited by 157 publications

References 35 publications

Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response

Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response

Cyclopentenone Prostaglandins Induce Lymphocyte Apoptosis by Activating the Mitochondrial Apoptosis Pathway Independent of External Death Receptor Signaling

Carcinogen-Induced Inflammation and Immunosuppression Are Enhanced in Xeroderma Pigmentosum Group A Model Mice Associated with Hyperproduction of Prostaglandin E2

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Prostaglandin D₂ affects the differentiation and functions of human dendritic cells: impact on the T cell response

Prostaglandin D₂ affects the differentiation and functions of human dendritic cells: impact on the T cell response