Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy

Harada, Yoshiteru; Hatanaka, Ko; Kawamura, Michiko; Saito, Maki; Ogino, Michiko; Murakami, Masataka; Ohno, Takashi; Ogino, Keiko; Yamamoto, Kei; Taketani, Yutaka; Yamamoto, Shozo; Kikuchi, Makoto

doi:10.1016/0090-6980(95)00168-9

Cited by 87 publications

(59 citation statements)

References 29 publications

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“…These observations suggest a functional linkage between COX-2 and mPGES. This idea is supported by the finding that specific COX-2 inhibitors reduce production of PGE 2 more than other stable PGs (27). Finally, our results provide an additional target by which glucocorticoids exert anti-inflammatory effects, because dexamethasone completely suppressed the induction of mPGES by IL-1␤.…”

Section: Discussionsupporting

confidence: 75%

Microsomal Prostaglandin E Synthase Is Regulated by Proinflammatory Cytokines and Glucocorticoids in Primary Rheumatoid Synovial Cells

Stichtenoth

Thorén

Bian

et al. 2001

The Journal of Immunology

245

214

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The selective induction of PGE2 synthesis in inflammation suggests that a PGE synthase may be linked to an inducible pathway for PG synthesis. We examined the expression of the recently cloned inducible microsomal PGE synthase (mPGES) in synoviocytes from patients with rheumatoid arthritis, its modulation by cytokines and dexamethasone, and its linkage to the inducible cyclooxygenase-2. Northern blot analysis showed that IL-1β or TNF-α treatment induces mPGES mRNA from very low levels at baseline to maximum levels at 24 h. IL-1β-induced mPGES mRNA was inhibited by dexamethasone in a dose-dependent fashion. Western blot analysis demonstrated that mPGES protein was induced by IL-1β, and maximum expression was sustained for up to 72 h. There was a coordinated up-regulation of cyclooxygenase-2 protein, although peak expression was earlier. Differential Western blot analysis of the microsomal and the cytosolic fractions revealed that the induced expression of mPGES protein was limited to the microsomal fraction. The detected mPGES protein was catalytically functional as indicated by a 3-fold increase of PGES activity in synoviocytes following treatment with IL-1β; this increased synthase activity was limited to the microsomal fraction. In summary, these data demonstrate an induction of mPGES in rheumatoid synoviocytes by proinflammatory cytokines. This novel pathway may be a target for therapeutic intervention for patients with arthritis.

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Section: Discussionsupporting

confidence: 75%

Microsomal Prostaglandin E Synthase Is Regulated by Proinflammatory Cytokines and Glucocorticoids in Primary Rheumatoid Synovial Cells

Stichtenoth

Thorén

Bian

et al. 2001

The Journal of Immunology

245

214

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“…The promoter region of the murine and human COX-2 genes contain binding sites for NF-B Topping and Jones, 1998), and there is evidence that 15d-PGJ 2 attenuates the expression of COX-2 in rat synoviocytes (Tsubouchi et al, 2001). An enhanced formation of prostanoids after the induction of COX-2 contributes to the pathophysiology of local and chronic inflammation (Harada et al, 1996;Cuzzocrea et al, 2000b) and selective inhibitors of COX-2 also exert potent anti-inflammatory effects (Futaki et al, 1993;Mitchell et al, 1993;Tomlinson et al, 1994;Harada et al, 1996). Here, we demonstrate that the increase in the levels of PGE 2 caused by injection of carrageenan into the pleural cavity of mice is reduced in the exudate of mice treated with 15d-PGJ 2 .…”

Section: Discussionmentioning

confidence: 60%

The Cyclopentenone Prostaglandin 15-Deoxy-Δ^12,14-Prostaglandin J₂Attenuates the Development of Acute and Chronic Inflammation

et al. 2002

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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligandactivated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. The PPAR-␥ receptor subtype seems to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxy-⌬ 12,14 -PGJ 2 (15d-PGJ 2 ), which is a metabolite of prostaglandin D 2 , functions as an endogenous ligand for PPAR-␥. We postulated that 15d-PGJ 2 would attenuate inflammation. In the present study, we have investigated the effects of 15d-PGJ 2 of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis, respectively) in animal models. We report for the first time, to our knowledge, that 15d-PGJ 2 (given at 10, 30, or 100 g/kg i.p. in the pleurisy model or at 30 g/kg i.p every 48 h in the arthritis model) exerts potent antiinflammatory effects (e.g., inhibition of pleural exudate formation, mononuclear cell infiltration, delayed development of clinical indicators, and histological injury) in vivo. Furthermore, 15d-PGJ 2 reduced the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase and the expression of inducible nitric-oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated mice and in the joints from collagen-treated mice. Thus, 15d-PGJ 2 reduces the development of acute and chronic inflammation. Therefore, the cyclopentenone prostaglandin 15d-PGJ 2 may be useful in the therapy of acute and chronic inflammation.

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“…mPGES is an inducible enzyme that is highly expressed in the reproductive organs and is coordinately induced and functionally coupled with COX-II (Jakobsson et al 1999, Murakami et al 2000. The COX-II inhibitor reduces PGE 2 generation in rat carrageenin-induced pleurisy more profoundly than other PGs (Harada et al 1996). Ovarian follicular fluid after the ovulatory LH surge shows a distinct increase in PGE 2 production (Brown & Poyser 1984) and PGE 2 treatment restores anovulation in COX-II-deficient mice (BenEzra 1978).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

Sakurai¹,

Tamura²,

Kuroda³

2004

Journal of Endocrinology

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Vascular endothelial growth factor (VEGF) is known to be necessary for the vascularization of the developing corpus luteum. Our recent data suggested that cyclooxygenase-II (COX-II) may play a role in the formation of vascular plexuses in developing corpora lutea of the rat. Here we examined the relationship between VEGF and the expression of prostaglandin (PG)-metabolizing enzymes in rat ovarian luteal cells. VEGF treatment caused a dosedependent increase in the expression of COX-II and membrane-associated PGE synthase (mPGES) mRNA in cultured rat luteal cells. However, pretreatment of the luteal cells with a selective COX-II inhibitor, NS-398, abolished the VEGF-enhanced mPGES mRNA expression. VEGF also increased PGE 2 secretion. Conversely, PGE 2 dose-dependently stimulated VEGF mRNA expression. Furthermore, VEGF induced VEGF mRNA expression, but this effect was abolished by NS-398 pretreatment. These findings suggest that VEGF enhances PGE 2 production by stimulating COX-II and mPGES expression in rat corpus luteum and that the effect of VEGF on luteal cells may be partially mediated by this stimulation of PGE 2 production.

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Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy

Cited by 87 publications

References 29 publications

Microsomal Prostaglandin E Synthase Is Regulated by Proinflammatory Cytokines and Glucocorticoids in Primary Rheumatoid Synovial Cells

Microsomal Prostaglandin E Synthase Is Regulated by Proinflammatory Cytokines and Glucocorticoids in Primary Rheumatoid Synovial Cells

The Cyclopentenone Prostaglandin 15-Deoxy-Δ^12,14-Prostaglandin J₂Attenuates the Development of Acute and Chronic Inflammation

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

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Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy

Cited by 87 publications

References 29 publications

Microsomal Prostaglandin E Synthase Is Regulated by Proinflammatory Cytokines and Glucocorticoids in Primary Rheumatoid Synovial Cells

Microsomal Prostaglandin E Synthase Is Regulated by Proinflammatory Cytokines and Glucocorticoids in Primary Rheumatoid Synovial Cells

The Cyclopentenone Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2Attenuates the Development of Acute and Chronic Inflammation

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

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The Cyclopentenone Prostaglandin 15-Deoxy-Δ^12,14-Prostaglandin J₂Attenuates the Development of Acute and Chronic Inflammation