COX-1 and COX-2 contribute differentially to the LPS-induced release of PGE2 and TxA2 in liver macrophages

Bezugla, Yevgeniya; Kolada, Angelika; Kamionka, Sabine; Bernard, Brigitte; Scheibe, Roland; Dieter, Peter

doi:10.1016/j.prostaglandins.2005.11.001

Cited by 52 publications

(37 citation statements)

References 19 publications

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“…Chem. 31,2012In humans, dexamethasone provides its therapeutic antiinflammatory benefit by acting on specific molecular targets, including the glucocorticoid receptor annexin, prostaglandin endoperoxide synthase 1, and prostaglandin endoperoxide synthase 2 [39][40][41]. Through gene expression analyses, annexin and prostaglandin endoperoxide synthase mRNA have been identified in the ovarian tissue of various fish species, providing evidence of potential involvement of these genes in gonad differentiation and ovulation, respectively [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

Effects of a glucocorticoid receptor agonist, dexamethasone, on fathead minnow reproduction, growth, and development

LaLone

Villeneuve

Olmstead

et al. 2012

Enviro Toxic and Chemistry

102

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Synthetic glucocorticoids are pharmaceutical compounds prescribed in human and veterinary medicine as anti-inflammatory agents and have the potential to contaminate natural watersheds via inputs from wastewater treatment facilities and confined animal-feeding operations. Despite this, few studies have examined the effects of this class of chemicals on aquatic vertebrates. To generate data to assess potential risk to the aquatic environment, we used fathead minnow 21-d reproduction and 29-d embryo-larvae assays to determine reproductive toxicity and early-life-stage effects of dexamethasone. Exposure to 500 µg dexamethasone/L in the 21-d test caused reductions in fathead minnow fecundity and female plasma estradiol concentrations and increased the occurrence of abnormally hatched fry. Female fish exposed to 500 µg dexamethasone/L also displayed a significant increase in plasma vitellogenin protein levels, possibly because of decreased spawning. A decrease in vitellogenin messenger ribonucleic acid (mRNA) expression in liver tissue from females exposed to the high dexamethasone concentration lends support to this hypothesis. Histological results indicate that a 29-d embryo-larval exposure to 500 µg dexamethasone/L caused a significant increase in deformed gill opercula. Fry exposed to 500 µg dexamethasone/L for 29 d also exhibited a significant reduction in weight and length compared with control fry. Taken together, these results indicate that nonlethal concentrations of a model glucocorticoid receptor agonist can impair fish reproduction, growth, and development.

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Section: Discussionmentioning

confidence: 99%

Effects of a glucocorticoid receptor agonist, dexamethasone, on fathead minnow reproduction, growth, and development

LaLone

Villeneuve

Olmstead

et al. 2012

Enviro Toxic and Chemistry

102

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“…There is an increase in TXB2 in the portal hypertensive group with COX 2 inhibition, in which a decreased IHT was observed. Factors like trauma-hemorrhage, shear stress and pressure variations or lipopolysaccharide can modify TXA2 synthesis in the liver or in endothelial cells [19][20][21] . The increased TXB2 was not modified by treatment with ULDA.…”

Section: Discussionmentioning

confidence: 99%

Modifications produced by selective inhibitors of cyclooxygenase and ultra low dose aspirin on platelet activity in portal hypertension

Eizayaga

Aguejouf²,

Desplat³

et al. 2007

WJG

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INTRODUCTIONPortal hypertension is a major complication of chronic liver disease. In its pathophysiology, increased hepatic resistance is followed by a hyperdynamic circulatory state [1] . This hyperdynamic state, in which nitric oxide (NO) and prosatcyclin (PGI2) are important vasoactive substances, induces a decreased platelet activity, even in the absence of hepatic damage. Although NO plays an important role in modifying platelet adhesion in portal hypertension [2] , PGI2, a powerful vasodilator prostanoid with antithrombotic properties, was also found increased in mesenteric vascular bed [3] . Ultra low dose aspirin (ULDA) has shown prothrombotic activity when analysed in humans and in the interface platelet-endothelial cell [4,5] . Previous papers have shown the potentially beneficial effect of ULDA in portal hypertensive animals normalizing altered platelet activity and induced hemorrhagic time [6] . Further experiments were performed to clarify if this effect was mediated mostly by a cyclooxigenase (COX) pathway or by modifying NO synthesis, the two aspirin mechanisms of action [7] , although a previous study with a different model suggested that ULDA could decrease PGI2 synthesis [8] . The same in vivo Laser induced thrombus formation, was used in portal hypertensive rats to investigate the effects of Indomethacin, a non selective COX inhibitor, and L-Nitro Arginin Methyl Ester (NAME), a non selective inhibitor of NO production. The results suggested that the effects of ULDA were more influenced by COX pathway than by NO synthesis inhibition [9] . Addition of ULDA in portal hypertensive rats, when previously inhibiting COX with Indomethacin, increased number of emboli and duration Abstract AIM: To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo. METHODS:Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1α, TXB2, PGE2 and LTB4 were also performed. RESULTS:The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1α was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged. CONCLUSION:These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats, could act through a COX 2

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“…There are three PGE synthases membrane PGE synthase 1 (mPGES1), mPGES2, cPGES. Although all can convert PGH 2 into PGE 2 , only mPGES1 has been shown to be responsible for induction of PGE 2 from macrophages (16,17). The ability of PGE 2 to block T cell proliferation is mediated through the E prostanoid receptor 4 (18).…”

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confidence: 99%

Francisella tularensis-Infected Macrophages Release Prostaglandin E2 that Blocks T Cell Proliferation and Promotes a Th2-Like Response

Woolard

Wilson

Hensley

et al. 2007

The Journal of Immunology

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Francisella tularensis is a highly infectious bacterial pathogen, and is likely to have evolved strategies to evade and subvert the host immune response. In this study, we show that F. tularensis infection of macrophages alters T cell responses in vitro, by blocking T cell proliferation and promoting a Th2-like response. We demonstrate that a soluble mediator is responsible for this effect and identify it as PGE2. Supernatants from F. tularensis-infected macrophages inhibited IL-2 secretion from both MHC class I and MHC class II-restricted T cell hybridomas, as well as enhanced a Th2-like response by inducing increased production of IL-5. Furthermore, the soluble mediator blocked proliferation of naive MHC class I-restricted T cells when stimulated with cognate tetramer. Indomethacin treatment partially restored T cell proliferation and lowered IL-5 production to wild-type levels. Macrophages produced PGE2 when infected with F. tularensis, and treatment of infected macrophages with indomethacin, a cyclooxygenase-1/cyclooxygenase-2 inhibitor, blocked PGE2 production. To further demonstrate that PGE2 was responsible for skewing of T cell responses, we infected macrophages from membrane PGE synthase 1 knockout mice (mPGES1−/−) that cannot produce PGE2. Supernatants from F. tularensis-infected membrane PGE synthase 1−/− macrophages did not inhibit T cell proliferation. Furthermore, treatment of T cells with PGE2 recreated the effects seen with infected supernatant. From these data, we conclude that F. tularensis can alter host T cell responses by causing macrophages to produce PGE2. This study defines a previously unknown mechanism used by F. tularensis to modulate adaptive immunity.

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COX-1 and COX-2 contribute differentially to the LPS-induced release of PGE2 and TxA2 in liver macrophages

Cited by 52 publications

References 19 publications

Effects of a glucocorticoid receptor agonist, dexamethasone, on fathead minnow reproduction, growth, and development

Effects of a glucocorticoid receptor agonist, dexamethasone, on fathead minnow reproduction, growth, and development

Modifications produced by selective inhibitors of cyclooxygenase and ultra low dose aspirin on platelet activity in portal hypertension

Francisella tularensis-Infected Macrophages Release Prostaglandin E2 that Blocks T Cell Proliferation and Promotes a Th2-Like Response

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