Mechanisms of prostaglandin E2‐induced interleukin‐6 release in astrocytes: possible involvement of EP4‐like receptors, p38 mitogen‐activated protein kinase and protein kinase C

Fiebich, Bernd L.; Schleicher, Sandra; Spleiss, Olivia; Czygan, Martin; Hüll, Michael

doi:10.1046/j.1471-4159.2001.00652.x

Cited by 120 publications

(74 citation statements)

References 50 publications

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“…EP4, one of the receptors for PGE 2 , increases intracellular cAMP levels via activation of adenylate cyclase and promotes activation of the PKA, PI3K, p38 MAPK, and MAPKK pathways (22)(23)(24)(25). The present study demonstrated that a specific EP4 agonist and 8-Br-cAMP both enhanced mTREM-1 gene expression, while inhibitors of PKA, p38 MAPK, and PI3K blocked the PGE 2 -induced increase of mTREM-1 expression.…”

Section: Figuresupporting

confidence: 60%

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Lipopolysaccharide-Induced Up-Regulation of Triggering Receptor Expressed on Myeloid Cells-1 Expression on Macrophages Is Regulated by Endogenous Prostaglandin E2

Murakami

Kohsaka

Kitasato

et al. 2007

The Journal of Immunology

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface molecule that is expressed by neutrophils and monocytes. TREM-1 expression is modulated by various ligands for TLRs in vitro and in vivo. However, the influence of PGE2, a potential mediator of inflammation, on TREM-1 expression has not been elucidated. In this study, we examined the effects of PGE2 on LPS-induced TREM-1 expression by resident murine peritoneal macrophages (RPM) and human PBMC. PGE2 significantly induced murine TREM-1 (mTREM-1) expression by RPM. Up-regulation of TREM-1 expression was specific to PGE2 among arachidonic acid metabolites, while ligands for chemoattractant receptor-homologous molecule expressed on Th2 cells and the thomboxane-like prostanoid receptor failed to induce mTREM-1 expression. PGE2 also increased expression of the soluble form of TREM-1 by PBMC. LPS-induced TREM-1 expression was regulated by endogenous PGE2 especially in late phase (>2 h after stimulation), because cyclooxygenase-1 and -2 inhibitors abolished this effect at that points. A synthetic EP4 agonist and 8-Br-cAMP also enhanced mTREM-1 expression by RPM. Furthermore, protein kinase A, PI3K, and p38 MAPK inhibitors prevented PGE2-induced mTREM-1 expression by RPM. Activation of TREM-1 expressed on PGE2-pretreated PBMC by an agonistic TREM-1 mAb significantly enhanced the production of IL-8 and TNF-α. These findings indicate that LPS-induced TREM-1 expression on macrophages is mediated, at least partly, by endogenous PGE2 followed by EP4 and cAMP, protein kinase A, p38 MAPK, and PI3K-mediated signaling. Regulation of TREM-1 and the soluble form of TREM-1 expression by PGE2 may modulate the inflammatory response to microbial pathogens.

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Section: Figuresupporting

confidence: 60%

“…Intracellular cAMP is a major regulator of PKA (22) and cAMP also activates the PI3K-, p38 MAPK-, and ERK-signaling pathways (23)(24)(25). Therefore, we investigated the signaling pathways involved in PGE 2 -induced expression of TREM-1 by using synthetic inhibitors of these kinases.…”

Section: Blocking Of Pka P38 Mapk and Pi3k Inhibits Pge 2 -Induced mentioning

confidence: 99%

Lipopolysaccharide-Induced Up-Regulation of Triggering Receptor Expressed on Myeloid Cells-1 Expression on Macrophages Is Regulated by Endogenous Prostaglandin E2

Murakami

Kohsaka

Kitasato

et al. 2007

The Journal of Immunology

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“…1, it is likely that PGD 2 /E 2 acts upstream of PKC jointly with AA. Activation of PKC by PGE 2 is known in a certain cell type (42). However, the possibility that PGD 2 /E 2 acts on AMPARs in parallel with PKC (P2 in Fig.…”

Section: Resultsmentioning

confidence: 98%

Lipid signaling in cytosolic phospholipase A ₂ α–cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning

Shirai²,

Okamoto³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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In this study, we show the crucial roles of lipid signaling in longterm depression (LTD), that is, synaptic plasticity prevailing in cerebellar Purkinje cells. In mouse brain slices, we found that cPLA 2 α knockout blocked LTD induction, which was rescued by replenishing arachidonic acid (AA) or prostaglandin (PG) D 2 or E 2 . Moreover, cyclooxygenase (COX)-2 inhibitors block LTD, which is rescued by supplementing PGD 2 /E 2 . The blockade or rescue occurs when these reagents are applied within a time window of 5-15 min following the onset of LTD-inducing stimulation. Furthermore, PGD 2 /E 2 facilitates the chemical induction of LTD by a PKC activator but is unable to rescue the LTD blocked by a PKC inhibitor. We conclude that PGD 2 /E 2 mediates LTD jointly with PKC, and suggest possible pathways for their interaction. Finally, we demonstrate in awake mice that cPLA 2 α deficiency or COX-2 inhibition attenuates short-term adaptation of optokinetic eye movements, supporting the view that LTD underlies motor learning.

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“…Because Tat interacts with astrocytes resulting in gliosis (18,70,71), it is tempting to speculate that Tat induces this activation through COX-2-derived prostaglandins. In this sense, it is worth mentioning that PGE 2 acts in an autocrine manner to alter astrocyte morphology and function (72,73). Thus, it is possible that some of those effects of Tat are mediated through COX-2 induction.…”

Section: Discussionmentioning

confidence: 99%

Extracellular HIV-Tat Induces Cyclooxygenase-2 in Glial Cells through Activation of Nuclear Factor of Activated T Cells

Blanco

Álvarez

Fresno

et al. 2008

The Journal of Immunology

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Both the HIV-1 protein Tat and cyclooxygenase-2 (COX-2) have been involved in the neuropathogenesis associated with HIV-1 infection. However, the relationship among them has not been addressed. Here, we found that extracellular Tat was able to induce COX-2 mRNA and protein expression and PGE2 synthesis in astrocytoma cell lines and primary human astrocytes. Moreover, Tat induced COX-2 promoter transcription. Deletion of NF-κB sites of the promoter did not diminish Tat-dependent transcription. Interestingly, Tat did not induce NF-κB activity, suggesting that NF-κB was not necessary to control COX-2 transcription induced by Tat. In contrast, deletion or mutation of the NFAT and/or AP-1 site abrogated COX-2 induction by Tat. Moreover, Tat induced transcription of NFAT- and AP-1-dependent reporter genes. Transfection of a dominant negative c-Jun mutant protein, TAM-67, or of a dominant negative version of NFAT, efficiently blocked the induction of COX-2 promoter by Tat, confirming the requirement of both transcription factors. Moreover, Tat induced NFAT translocation to the nucleus and binding to the distal site of the COX-2 promoter. The importance of NFAT and AP-1 in COX-2 induction and PGE2 synthesis by Tat was corroborated by using pharmacological inhibitors of the NFΑΤ, ERK, and JNK pathways. In summary, our results indicate that HIV-1 Tat was able to induce COX-2 and PGE2 synthesis in astrocytic cells through an NFAT/AP-1-dependent mechanism.

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Mechanisms of prostaglandin E2‐induced interleukin‐6 release in astrocytes: possible involvement of EP4‐like receptors, p38 mitogen‐activated protein kinase and protein kinase C

Cited by 120 publications

References 50 publications

Lipopolysaccharide-Induced Up-Regulation of Triggering Receptor Expressed on Myeloid Cells-1 Expression on Macrophages Is Regulated by Endogenous Prostaglandin E2

Lipopolysaccharide-Induced Up-Regulation of Triggering Receptor Expressed on Myeloid Cells-1 Expression on Macrophages Is Regulated by Endogenous Prostaglandin E2

Lipid signaling in cytosolic phospholipase A ₂ α–cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning

Extracellular HIV-Tat Induces Cyclooxygenase-2 in Glial Cells through Activation of Nuclear Factor of Activated T Cells

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Mechanisms of prostaglandin E2‐induced interleukin‐6 release in astrocytes: possible involvement of EP4‐like receptors, p38 mitogen‐activated protein kinase and protein kinase C

Cited by 120 publications

References 50 publications

Lipopolysaccharide-Induced Up-Regulation of Triggering Receptor Expressed on Myeloid Cells-1 Expression on Macrophages Is Regulated by Endogenous Prostaglandin E2

Lipopolysaccharide-Induced Up-Regulation of Triggering Receptor Expressed on Myeloid Cells-1 Expression on Macrophages Is Regulated by Endogenous Prostaglandin E2

Lipid signaling in cytosolic phospholipase A 2 α–cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning

Extracellular HIV-Tat Induces Cyclooxygenase-2 in Glial Cells through Activation of Nuclear Factor of Activated T Cells

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Lipid signaling in cytosolic phospholipase A ₂ α–cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning