共查询到20条相似文献,搜索用时 15 毫秒
1.
Bernd L. Fiebich Michael Hüll Klaus Lieb Karin Gyufko Mathias Berger Joachim Bauer 《Journal of neurochemistry》1997,68(2):704-709
Abstract: Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD) and prion diseases. Nonsteroidal antiinflammatory drugs (NSAIDs), potent inhibitors of PG synthesis, appear to be beneficial in the treatment of AD. To assess whether PGs are able to induce IL-6 synthesis in cells of the CNS, IL-6 mRNA and protein syntheses were measured in a human astrocytoma cell line after stimulation with different PGs. PGE1 and PGE2 , but not PGD2 and PGF2α , led to a rapid and transient induction of IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1β-induced IL-6 mRNA synthesis. These results are discussed with respect to the participation of PGs in neurodegenerative diseases (and its inhibition by NSAIDs) by affecting cytokine expression. 相似文献
2.
DAVID W. STANLEY-SAMUELSON JOHN J. PELOQUIN WERNER LOHER 《Physiological Entomology》1986,11(2):213-219
ABSTRACT. We report the effects of prostaglandin (PG) injection on egg-laying by sexually mature virgin crickets, Teleogryllus commodus Walker. High egg-laying activity is associated with PGE1 PGE2 , 6-keto-PGE1 and 15-keto-PGE2 , compounds that share the basic prostanoid backbone (C20 substituted fatty acid, 5 membered ring, a 7- and an 8-carbon aliphatic chain), and 9-keto, 11-hydroxyl ring substitutions. PGs without these ring features and other compounds that lack the prostanoid backbone have no or only intermediate egg-laying effects. Adding oxygen functionalities or an aliphatic double bond tends to increase egg-laying activity. Hence, 15-keto-PGF2 and TxB2 , both of which have an additional backbone oxygen compared with their less active analogues, are highly active compounds. Two of the most active PGs, 15-keto-PGE2 and 15-keto-PGE2α , are the products of inactivating metabolism in mammalian systems, describing a fundamental difference in PG biochemistry with respect to mammals and insects. 相似文献
3.
† M. Kerry O'Banion †Janice C. Miller †Julia W. Chang ‡Mitchell D. Kaplan †Paul D. Coleman 《Journal of neurochemistry》1996,66(6):2532-2540
Abstract: Activation of glial cells and the consequent release of cytokines, proteins, and other intercellular signaling molecules is a well-recognized phenomenon in brain injury and neurodegenerative disease. We and others have previously described an inducible prostaglandin G/H synthase, known as PGHS-2 or cyclooxygenase-2, that is up-regulated in many cell systems by cytokines and growth factors and down-regulated by glucocorticoid hormones. In cultured mouse astrocytes we observed increased production of prostaglandin E2 (PGE2 ) after stimulation with either interleukin-1β (IL-1β) or the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). This increase in PGE2 content was blocked by pretreatment with dexamethasone and correlated with increases in cyclooxygenase activity measured at 4 h. Northern blots revealed concomitant increases in PGHS-2 mRNA levels that peaked at 2 h and were dependent on the dosage of IL-1β. Dexamethasone inhibited this induction of PGHS-2 mRNA by IL-1β. TPA, basic fibroblast growth factor, and the proinflammatory factors tumor necrosis factor α and lipopolysaccharide, but not interleukin-6, also stimulated PGHS-2 mRNA expression. Relative to IL-1β, the greater increases in PGE2 production and cyclooxygenase activity caused by TPA correlated with a greater induction of PGHS-2 mRNA. Furthermore, NS-398, a specific inhibitor of cyclooxygenase-2, blocked >80% of the cyclooxygenase activity in TPA-treated astrocytes. These findings indicate that increased expression of PGHS-2 contributes to prostaglandin production in cultured astrocytes exposed to cytokines and other factors. 相似文献
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5.
Culture supernatants from dogfish leucocytes, exposed to the Ca2+ ionophore A23187, were analyzed for eicosanoid production by gas chromatography-electron capture mass spectrometry. Consistently high levels of the prostaglandins (PG) D2 , F2α and E2 were produced, while thromboxane B2 and leukotriene B4 were found in smaller amounts. No 6-oxo PGF1α , a degradation product of prostacyclin, or 13,14-dihydro-15-oxo-PGF2α , a metabolite of PGE2 and PGF2α , were detected. The results are compared with similar experiments using mammalian leucocytes. 相似文献
6.
7.
V. Tomasi Carla Biondi A. Trevisani Marta Martini V. Perri 《Journal of neurochemistry》1977,28(6):1289-1297
Abstract— Dopamine, norepinephrine, carbamylcholine and PGE1 (prostaglandin E1 ). increased cyclic AMP concentrations in slices of bovine superior cervical ganglia. PGF1α was less effective and neither PGE2 nor PGF2α had any effect. Dopamine and PGE, alone or in combination, did not modify low K m cyclic AMP phosphodiesterase activity. Combinations of dopamine and PGE, showed a marked synergistic effect, increasing ganglionic cyclic AMP to a much greater extent than that observed when the two compounds were tested alone. Norepinephrine (10 μ M) , which increased cyclic AMP as much as 10 μ m -dopamine, showed no synergistic effect when tested in the presence of PGE1 or other PGs. Phentolamine, fluphenazine and triflupromazine blocked the dopamine effect without suppressing its synergism with PGE1 Adenylate cyclase of synaptosomes isolated from the ganglia under a variety of experimental conditions appeared to be as responsive to PGE1 as the slices, but it was poorly stimulated by dopamine and was not synergistically modulated by dopamine in the presence of PGE1
These and other data are interpreted as indicating the presence of both a PGE1 -sensitive and a PGE1 -modulated dopamine-sensitive adenylate cyclase in the cervical ganglion. These adenylate cyclases are tentatively assigned to pre- and post-synaptic structures respectively. 相似文献
These and other data are interpreted as indicating the presence of both a PGE
8.
Abstract: 45 Ca2+ uptake measurements were performed on intact and osmotically lysed synaptosomes from rat brain to study the possible influence of prostaglandins (PGs) on Ca2+ movements into and within the nerve endings. The K+ -induced 45 Ca2+ uptake of intact synaptosomes was not influenced by several inhibitors of PG synthesis. 45 Ca2+ uptake in lysed synaptosomal preparations was promoted by ATP and seemed to be largely attributable to mitochondria, as it was inhibited by mitochondrial poisons. This Ca2+ uptake was strongly reduced by PG synthesis inhibitors but also by PG precursor fatty acids. Both PG synthesis inhibitors and precursors, according to their relative efficacy in blocking Ca2+ uptake, were able to induce Ca2+ efflux from preloaded intrasynaptosomal organelles. The PGs E2 , F2α , D2 , and thromboxane B2 were without effect on 45 Ca2+ uptake in lysed synaptosomal preparations. On the basis of our results it does not seem likely that PGs influence Ca2+ availability by modulating Ca2+ fluxes into or within the nerve endings. The observed inhibitory effects of PG synthesis inhibitors and precursors on the intrasynaptosomal Ca2+ uptake might be due to unspecific impairment of mitochondrial functions. 相似文献
9.
Il-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production 总被引:6,自引:0,他引:6
Berg DJ Zhang J Lauricella DM Moore SA 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(4):2674-2680
IL-10 is a potent anti-inflammatory and immune regulatory cytokine. IL-10(-/-) mice produce exaggerated amounts of inflammatory cytokines when stimulated with LPS, indicating that endogenous IL-10 is a central regulator of inflammatory cytokine production in vivo. PGs are lipid mediators that are also produced in large amounts during the inflammatory response. To study the role of IL-10 in the regulation of PG production during the acute inflammatory response, we evaluated LPS-induced cyclooxygenase (COX) expression and PG production in wild-type (wt) and IL-10(-/-) mice. LPS-induced PGE(2) production from IL-10(-/-) spleen cells was 5.6-fold greater than that from wt spleen cells. LPS stimulation resulted in the induction of COX-2 mRNA and protein in both wt and IL-10(-/-) spleen cells; however, the magnitude of increase in COX-2 mRNA was 5.5-fold greater in IL-10(-/-) mice as compared with wt mice. COX-1 protein levels were not affected by LPS stimulation in either wt or IL-10(-/-) mice. Neutralization of IFN-gamma, TNF-alpha, or IL-12 markedly decreased the induction of COX-2 in IL-10(-/-) spleen cells, suggesting that increased inflammatory cytokine production mediates much of the COX-2 induction in IL-10(-/-) mice. Treatment of IL-10(-/-) mice with low doses of LPS resulted in a marked induction of COX-2 mRNA in the spleen, whereas wt mice had minimal expression of COX-2 mRNA. These findings indicate that, in addition to IL-10's central role in the regulation of inflammatory cytokines, endogenous IL-10 is an important regulator of PG production in the response to LPS. 相似文献
10.
W.B Ross H.A. Leaver P.L. Yap G.M. Raab B.H. Su D.C. Carter 《FEMS microbiology letters》1990,64(5-6):321-325
Abstract The transfusion of blood is associated with long-term immunosuppression, which has been postulated to influence immunosurveillance and cancer cell killing. The mononuclear phagocyte synthesises large quantities of PGE2 , and PGE2 has been shown to inhibit the activity of a range of immunocompetent cell types. The role of mononuclear phagocyte PGE2 synthesis in transfusion-associated immunosuppression, and the elements of transfused blood which control this immunosuppression, were investigated using a transfused rat model. A significant increase in macrophage PGE2 synthesis was detected 7 days after transfusion with blood and serum. The storage of blood for 24 h increased the stimulatory activity of transfused blood. The effects of storage and serum on macrophage PGE2 synthesis were greater than effects due to genetic differences between blood donor and recipient, and the serum effects indicated that a major factor activating PGE2 -mediated immunosuppression in transfused subjects may be humoral in nature. 相似文献
11.
Regional Prostaglandin Levels in Cerebral Ischaemia 总被引:1,自引:1,他引:0
H. Alan Crockard Kishore K. Bhakoo Peter T. Lascelles 《Journal of neurochemistry》1982,38(5):1311-1314
Abstract: Regional quantitative studies of brain prostaglandins (PG) in gerbils with bilateral carotid ligation have shown increases in PG2α in all areas of ischaemia but with no increases in PGE2 . Pretreatment of animals with indomethacin (3 mg/kg) reduced this response, whereas dexamethasone (2.5 mg/kg) had no such effect. PGE1 and thromboxane-B2 were found not to be present in our preparation. The significance of these findings lies in the fact that both drugs, which are known to inhibit the development of ischaemic oedema, have now been shown to produce markedly different effects on prostaglandin levels. This may indicate either, that prostaglandins are not involved in is chaemic oedema formation, or, that the drugs have different mechanisms of action. 相似文献
12.
Five strains of filamentous fungi belonging to the genera Mortierella and Cunninghamella were examined for the content of dihomo-γ-linolenic, arachidonic, eicosapentaenoic acids and prostaglandins (type E2 and F 2α ). Prostaglandins were detected using an ELISA method in mycelia of all tested strains (range 50–4800 ng g−1 of PGE2 and 6–30 ng g−1 of PG F 2α ). Several micro-organisms also produced prostaglandins in the culture medium (2·2–137·6 μg l−1 for PGE2 and 0·4–7·8 μg l−1 for PG F 2α ). 相似文献
13.
Dmitry Gerashchenko Carsten T. Beuckmann †Yoshihide Kanaoka †‡§Naomi Eguchi William C. Gordon †Yoshihiro Urade Nicolas G. Bazan Osamu Hayaishi 《Journal of neurochemistry》1998,71(3):937-945
Abstract: Prostaglandin (PG) D2 is one of the major prostanoids in the mammalian brain and eye tissues. Its function is mediated by the prostanoid DP receptor, which is specific for PGD2 among the various prostanoids. In this study, we cloned the full-length cDNA for the rat DP receptor and used it for detection of DP receptor mRNA in various rat tissues. Northern blotting and RT-PCR analyses revealed that this DP receptor was expressed most intensely in the eye tissues, moderately in the leptomeninges and oviduct, and weakly in the epididymis. The tissue distribution profile of the mRNA for the rat DP receptor is overlapped with those of hematopoietic and lipocalin-type PGD synthases. Among rat eye tissues, the expression was the highest in the iris. In situ hybridization and in situ RT-PCR revealed DP receptor mRNA to be localized in the epithelium of the iris and ciliary body and in photoreceptor cells of the retina, suggesting the involvement of the receptor in the physiological regulation of intraocular pressure and the vision process. In the brain, DP receptor mRNA was dominantly expressed in the leptomeninges and was not detected in the brain parenchyma including the ventral rostral forebrain, the surface area of which is reportedly involved in sleep induction by PGD2 . 相似文献
14.
Fujiko Ozawa Yoshitoshi Kasuya Hiroshi Hama Sachie Asada Tetsuo Inada Katsutoshi Goto 《Journal of neurochemistry》1997,69(2):562-569
Abstract: We investigated the effect of cytoskeleton modulators on endothelin-B (ETB ) receptor expression in rat primary cultured astrocytes. Northern blot analysis and a binding study revealed that colchicine and nocodazole, microtubule-disrupting agents, decreased the levels of both ETB receptor mRNA and the number of ET-1 binding sites in quiescent astrocytes. Down-regulation of both ETB receptor mRNA and the number of binding sites for ET-1 was also observed in quiescent astrocytes treated with taxol, a microtubule-stabilizing agent. In contrast, neither β-lumicolchicine, an inactive isomer of colchicine, nor cytochalasin D, a microfilament-disrupting agent, influenced ETB receptor expression. The level of ETB receptors in astrocytes was affected by the cell state, namely, proliferative, quiescent, or differentiated state. The order of ETB receptor expression according to the cell state was proliferative state < quiescent state ≪ differentiated state induced by dibutyryl cyclic AMP. Also, in proliferative astrocytes and differentiated astrocytes, colchicine significantly down-regulated both ETB receptor mRNA and the number of binding sites for ET-1. However, thymidine assay revealed that colchicine did not change quiescent astrocytes and differentiated astrocytes to a proliferative state. Furthermore, the increase in glutamine synthetase activity in differentiated astrocytes was not affected by colchicine. These results suggest that microtubule dynamics possibly regulates ETB receptor expression in astrocytes without affecting the cell state. 相似文献
15.
Abstract: The effect of phloretin on prostaglandin (PG) F2α -induced phosphoinositide hydrolysis and elevation of intracellular Ca2+ concentration was examined in cultured rat astrocytes. Phloretin inhibited PGF2α (1 μ M )-induced phosphoinositide hydrolysis in a concentration-dependent manner with an IC50 value of 16 μ M . The inhibitory action of phloretin was specific for PGs. The addition of increasing concentrations of phloretin caused progressive shifts of the dose-response curves of PGF2α to the right. In digitoninpermeabilized astrocytes, phloretin (100 μ M ) inhibited the stimulation induced by PGF2α (1 μ M ) plus GTPγS (50 μ M ) without affecting that induced by GTPγS alone. PGF2α at 1 μ M transiently increased astrocytic intracellular Ca2+ concentration in 39% of the cells tested. The response was completely blocked by 100 μ M phloretin and the calcium response recovered again after washing out phloretin. These results suggest that phloretin is an antagonist of PGF2α receptor linked to phospholipase C in astrocytes. 相似文献
16.
Abstract: Monolayer cultures of neuroblastome × glioma hybrid (clonal) cell line NG108-15, synchronized by the isoleucine/glutamine deprivation method, showed maximal expression of opiate binding sities at the same point in the cell cycle at which prostaglandin E1 (PGE1 ) had a maximum stimulatory effect of cyclinc AMP synthesis. However, the capacity of enkephalin (D-Ala2 D-Leu5 ] to block the stimulation of cyclic AMP synthesis by PGE1 was not related to the number of opiate receptors expressed. The K1 for the inhibition of cyclic AMP synthesis by opioid peptides increased substanitilly during the period of the cell cycle at which maximal expression of opiate binding sites occurred, making the effectivel level of inhibition of adenylate cyclase activity by 0.1μM enkephalin [D-Al2 D-Leu3 ] the same throght the cell cycle. Data are presented to suggest the enkephalin receptor coupling to adenylate cyclase, via a GTP-binding protein, is maximal during G1 phase (which may approximate the state of the differentiated neuron) and minimal during S + G2 phase, just prior to cell division, when many receptors are uncoupled. 相似文献
17.
Hüll M Müksch B Akundi RS Waschbisch A Hoozemans JJ Veerhuis R Fiebich BL 《Neurochemistry international》2006,48(8):663-672
Prostaglandins (PGs) are generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2) and modulate several functions in the CNS such as the generation of fever, the sleep/wake cycle, and the perception of pain. Moreover, the induction of COX-2 and the generation of PGs has been linked to neuroinflammatory aspects of Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs (NSAIDs) that block COX enzymatic activity have been shown to reduce the incidence of AD in various epidemiological studies. While several reports investigated the expression of COX-2 in neurons and microglia, expression of COX-2 in astroglial cells has not been investigated in detail. Here we show that amyloid β peptide 25–35 (Aβ25–35) induces COX-2 mRNA and protein synthesis and a subsequent release of prostaglandin E2 (PGE2) in primary midbrain astrocytes. We further demonstrate that protein kinase C (PKC) is involved in Aβ25–35-induced COX-2/PGE2 synthesis. PKC-inhibitors prevent Aβ25–35-induced COX-2 and PGE2 synthesis. Furthermore Aβ25–35 rapidly induces the phosphorylation and enzymatic activation of PKC in primary rat midbrain glial cells and in primary human astrocytes from post mortem tissue. Our data suggest that the PKC isoforms and/or β are most probably involved in Aβ25–35-induced expression of COX-2 in midbrain astrocytes. The potential role of astroglial cells in the phagocytosis of amyloid and the involvement of PGs in this process suggests that a modulation of PGs synthesis may be a putative target in the prevention of amyloid deposition. 相似文献
18.
M E Gerritsen 《Federation proceedings》1987,46(1):47-53
Cultured rabbit coronary microvessel endothelial (RCME) cells have been used as an in vitro model to study the regulation of microvascular endothelial cell prostaglandin (PG) production by hormones, vasoactive drugs, and inflammatory mediators in an environment that can be tightly controlled and that is unaffected by interactions with other cell types, physical stimulation, or alterations in oxygenation. The most potent stimuli for RCME cell PG secretion were substances associated with inflammation, including histamine, interleukin 1, leukotriene D4, fMet-Leu-Phe, interferon-gamma, and exogenous phospholipases. Inhibition of calcium availability by lower [Ca2+]o or by treatment with calcium channel blockers reduced A23187-stimulated PG release but increased PG synthesis from exogenous arachidonic acid (AA). These observations suggest that Ca2+ may regulate several steps in the pathway leading to PG synthesis and release. Elevated intracellular [Ca2+] may, on the one hand, promote PG production by stimulating phospholipase A2 leading to AA release and, on the other hand, limit the magnitude of the response by increasing the rate of AA reacylation. Glucocorticoids reduce PG production by RCME cells via an action that requires new protein and mRNA synthesis and appears to involve the production of an endothelial cell-derived phospholipase inhibitory protein, or "endocortin." Thus, microvascular endothelial cells can both contribute to (by the release of PGs and possibly platelet-activating factor-acether) and limit (by the production of endocortins) the degree of a local inflammatory response in the heart. 相似文献
19.
Tanabe K Takai S Matsushima-Nishiwaki R Kato K Dohi S Kozawa O 《Journal of neurochemistry》2008,106(2):519-528
Dexmedetomidine (Dexmd), a potent and highly specific α2 adrenoreceptor agonist, is an efficient therapeutic agent for sedation. Dexmd has been recently reported to have a neuroprotective effect. Heat shock protein (HSP) 27, a low-molecular weight HSP has been shown to be expressed following cerebral ischemia in astrocytes but not in neurons. HSP27 expression is involved in ischemic tolerance of the brain. This study investigated the effect of Dexmd on HSP27 in rat C6 glioma cells. 12- O -tetradecanoylphorbol-13-actate (TPA), a direct activator of protein kinase C (PKC), stimulated the phosphorylation of HSP27 at Ser82, but not Ser15 in a time-dependent manner. Prostaglandin (PG) E1 or PGE2 which activates the adenylyl cyclase-cAMP system as well as forskolin and dibutyryl-cAMP, suppressed the TPA-induced phosphorylation of HSP27. Dexmd reversed the suppression of HSP27 phosphorylation by the adenylyl cyclase-cAMP system. Therefore, these results strongly suggest that Dexmd reverses the suppression of HSP27 phosphorylation by the adenylyl cyclase-cAMP system activation through the inhibition of its system in C6 cells. α2 Adrenoreceptor agonists may therefore show a neuroprotective effect through the modification of HSP27 phosphorylation induced by PKC activation. 相似文献
20.
Rouzer CA Kingsley PJ Wang H Zhang H Morrow JD Dey SK Marnett LJ 《The Journal of biological chemistry》2004,279(33):34256-34268
Comprehensive studies of prostaglandin (PG) synthesis in murine resident peritoneal macrophages (RPM) responding to bacterial lipopolysaccharide (LPS) revealed that the primary PGs produced by RPM were prostacyclin and PGE(2). Detectable increases in net PG formation occurred within the first hour, and maximal PG formation had occurred by 6-10 h after LPS addition. Free arachidonic acid levels rose and peaked at 1-2 h after LPS addition and then returned to baseline. Cyclooxygenase-2 (COX-2) and microsomal PGE synthase levels markedly increased upon exposure of RPM to LPS, with the most rapid increases in protein expression occurring 2-6 h after addition of the stimulus. RPM constitutively expressed high levels of COX-1. Studies using isoform-selective inhibitors and RPM from mice bearing targeted deletions of ptgs-1 and ptgs-2 demonstrated that COX-1 contributes significantly to PG synthesis in RPM, especially during the initial 1-2 h after LPS addition. Selective inhibition of either COX isoform resulted in increased secretion of tumor necrosis factor-alpha (TNF-alpha); however, this effect was much greater with the COX-1 than with the COX-2 inhibitor. These results demonstrate autocrine regulation of TNF-alpha secretion by endogenous PGs synthesized primarily by COX-1 in RPM and suggest that COX-1 may play a significant role in the regulation of the early response to endotoxemia. 相似文献