Prostaglandins as Physiological Immunoregulators

Plescia, Otto J.; Racis, S.

doi:10.1159/000318766

Cited by 17 publications

(7 citation statements)

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“…PGs are among the most potent proinflammatory and immunoregulatory agents, as they promote vasodilatation, edema formation, and neutrophil and monocyte/macrophage infiltration and modulate functional activities of T and B lymphocytes (Plescia and Racis, 1988) . On the other hand, TXA 2 is responsible for vasoconstriction, platelet aggregation, and coagulation (Chen et a) ., 1986) .…”

Section: Discussionmentioning

confidence: 99%

Induction of Prostanoid Biosynthesis by Bacterial Lipopolysaccharide and Isoproterenol in Rat Microglial Cultures

Minghetti

Levi

1995

Journal of Neurochemistry

175

127

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We have used purified microglial cultures obtained from neonatal rat cerebral cortex to investigate the ability of microglia to release prostanoids after exposure to bacterial lipopolysaccharide, a classic macrophage activator. Release of prostaglandin E2, prostaglandin D2, and thromboxane A2 was low in basal conditions and increased in a dose‐ and time‐dependent way upon lipopolysaccharide treatment (1–100 ng/ml), by a mechanism requiring de novo protein synthesis. When compared with astrocytes, microglial cells appeared to respond more effectively to lipopolysaccharide, being able to release prostanoids after exposure to a 100‐fold lower concentration of lipopolysaccharide. In addition to prostanoids, we also measured the release of leukotriene B4; although lipopolysaccharide failed to stimulate leukotriene B4 release by microglial cells, it doubled the basal production in astrocytes. Lipopolysaccharide enhanced the release of preloaded [3H]arachidonic acid from microglial membrane phospholipids by a mechanism inhibited by the protein synthesis inhibitor cycloheximide, which suggests that the increased availability of arachidonic acid contributed to the enhanced prostanoid production. Lipopolysaccharide, however, also stimulated prostanoid synthesis by inducing cyclooxygenase activity, as shown by determining the activity of newly synthesized enzyme after inactivating the endogenous enzyme with aspirin and by assessing the level of the inducible form of cyclooxygenase by western blot analysis. Among the mechanisms potentially involved in the regulation of microglial prostanoid production, we studied the effect of β‐adrenergic receptor activation. The β‐agonist isoproterenol was inactive by itself but doubled the effect of lipopolysaccharide. The drug appeared to act mainly through the inducible cyclooxygenase; because it did not stimulate arachidonic acid release, it enhanced the lipopolysaccharide‐evoked prostanoid production observed after aspirin pretreatment and induced de novo synthesis of cyclooxygenase detectable by western blot analysis. We suggest that during cerebral inflammatory processes microglia can contribute to the establishment of high prostanoid levels, which can be further elevated by β‐adrenergic activation.

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Section: Discussionmentioning

confidence: 99%

Induction of Prostanoid Biosynthesis by Bacterial Lipopolysaccharide and Isoproterenol in Rat Microglial Cultures

Minghetti

Levi

1995

Journal of Neurochemistry

175

127

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“…High levels of PGE2 have been shown to suppress immune surveillance (181)(182)(183) and to impair killing of malignant cells (184,185). These effects appear to be specific to PGE2 since other eicosanoids have not been shown to have a clear role in the regulation of cellular and humoral immune responses (186).…”

Section: Immune Modulationmentioning

confidence: 99%

Prostaglandins and cancer

Fischer

1997

Front Biosci

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Prostaglandins (PGs) are lipids produced enzymatically and nonenzymatically from 20 carbon fatty acids, particularly arachidonic acid. Prostaglandins and related metabolites (collectively referred to as eicosanoids), including the thromboxanes, prostacyclins, hydroperoxy and hydroxy fatty acids, and leukotrienes are produced by most tissues of the body by oxidation of arachidonic acid, although the amount and class of product varies with cell type. The biological action of many of these eicosanoids as key regulators of cell processes that range from proliferation to adhesion and migration are currently being elucidated. An association of high levels of PGs and their synthetic enzymes, the PG synthases/cyclooxygenases, have been noted for many of the major types of cancer. Prostaglandins may contribute to the cancer processes through one or more of several mechanisms including increased proliferation, apoptosis, enhanced carcinogen metabolism or modulation of the immune system. The recent understanding of the regulation of substrate availability and of the regulation (or dysregulation in many neoplasias) of the synthetic enzymes has opened avenues leading to the design of isozyme specific inhibitors and better cancer prevention strategies. However, the apoptosis caused by these inhibitors as well as other drugs has raised some question concerning the relative importance of PGs. This is an issue that remains to be resolved.

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“…Red cell FA composition is thought to reflect dietary FA intake (Dougherty et al, 1987). Likewise, eicosanoids, particularly PG, are known to regulate the activation and function of certain immune-active cells and excess amounts of PG are produced in tumor bearing animals in which suppression of immune responses occur (Plescia and Racis, 1988).…”

Section: In T R 0 Duct I 0 Nmentioning

confidence: 99%

Modification of Membrane Composition, Eicosanoid Metabolism, and Immunoresponsiveness by Dietary Omega‐3 and Omega‐6 Fatty Acid Sources, Modulators of Ultraviolet‐carcinogenesis

Fischer

Black

1991

Photochem & Photobiology

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Dietary sources of lipids containing predominantly n-3 or n-6 fatty acids (FA) have been examined for effect upon several potential pathophysiologic parameters. Epidermal, plasma, and red blood cell (RBC) membrane FA composition exhibited marked differences between animals fed the respective dietary lipid sources. Reduced levels of 18:1, 20:3 and 20:4 occurred in the n-3 FA fed animals which exhibited significantly higher levels of 20:5 and 22:6. Approximately equal levels of 18:2 were present in animals fed either diet. Despite marked differences in RBC membrane FA composition, only marginal effect upon osmotic fragility occurred. Lower levels of 20:3 and 20:4 found in n-3 fed animals could result from a deficit of elongase and/or delta 5-desaturase activity. Whether lower 20:4 levels in n-3 fed animals could rate-limit eicosanoid metabolism is unknown, but epidermal capacity to metabolise arachidonic acid in these animals was found to be closely related to n-6 FA intake. Animals fed n-3 FA exhibited markedly lower levels of plasma PGE2, even when the diet was supplemented with n-6 FA. In addition, UV-radiated animals receiving the n-3 FA source demonstrated a reduced (approximately 30%) response to inflammatory stimulus and a greater (4.5-fold) delayed hypersensitivity (DH) to dinitrochlorobenzene than animals fed the n-6 FA source. These data demonstrate that dietary lipid strongly influences tissue FA composition, eicosanoid metabolism, and, in the case of DH, at least one type of T-cell mediated immune response in UV-irradiated animals.

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Prostaglandins as Physiological Immunoregulators

Cited by 17 publications

References 0 publications

Induction of Prostanoid Biosynthesis by Bacterial Lipopolysaccharide and Isoproterenol in Rat Microglial Cultures

Induction of Prostanoid Biosynthesis by Bacterial Lipopolysaccharide and Isoproterenol in Rat Microglial Cultures

Prostaglandins and cancer

Modification of Membrane Composition, Eicosanoid Metabolism, and Immunoresponsiveness by Dietary Omega‐3 and Omega‐6 Fatty Acid Sources, Modulators of Ultraviolet‐carcinogenesis

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