Prostaglandin E2 (PGE2) Enhances Aged Hematopoietic Stem Cell Function
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE174346 | GEO | 2021/05/13
REPOSITORIES: GEO
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Project description:Prostaglandin E2 (PGE2) Enhances Aged Hematopoietic Stem Cell Function
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Project description:To determine how PGE2 treatment affects HDLECs, we treated cultured HDLECs with either a vehicle or 500 nM dmPGE2 for 16 hours
2023-09-12 | GSE223854 | GEO
Project description:The ECM propagates processes in idiopathic pulmonary fibrosis (IPF), leading to progressive lung scarring. We established an IPF-conditioned matrix (IPF-CM) system as a platform for testing drug candidates. Here, we tested the involvement of a PGE2 and PDE4 inhibitor, Roflumilast, in the IPF-CM system. Primary normal/IPF tissue-derived human lung fibroblasts (N/IPF-HLFs) were cultured on Matrigel and then removed to create the IPF-CM. N-HLFs were exposed to the IPF-CM/N-CM with/without PGE2 (1 nM) and Roflumilast (1 µM) for 24 h. The effect of the IPF-CM on cell phenotype and pro-fibrotic gene expression was tested. In addition, electronic records of 107 patients with up to 15-year follow-up were retrospectively reviewed. Patients were defined as slow/rapid progressors using forced vital capacity (FVC) annual decline. Medication exposure was examined. N-HLFs cultured on IPF-CM were arranged in large aggregates as a result of increased proliferation, migration and differentiation. A PGE2 and Roflumilast combination blocked the large aggregate formation induced by the IPF-CM (p < 0.001) as well as cell migration, proliferation, and pro-fibrotic gene expression. A review of patient records showed that significantly more slow-progressing patients were exposed to NSAIDs (p = 0.003). PGE2/PDE4 signaling may be involved in IPF progression. These findings should be further studied.
| S-EPMC10418473 | biostudies-literature
Project description:Severe asthma and sinus disease is a consequence of Type 2 inflammation (T2I), mediated by IL-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E2 (PGE2) drives production of sST2 to limit features of lung T2I. PGE2 deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE2 metabolites correlate with serum sST2. In mice, PGE2 enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs or EP2 receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE2 or ST2 expression by MCs back to control levels. PGE2 deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE2 thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE2 states.
2024-05-20 | GSE266501 | GEO
Project description:PGE2 is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE2, acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE2, we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes. Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependent inhibition of the expression of genes involved in the IFN-gamma activation pathway, including IFN-gamma itself. This effect of the PGE2/EP4 axis on IFN-gamma is a reciprocal phenomenon since IFN-gamma blocks PGE2 release and blocks EP receptor expression. The mutually antagonistic relationship between IFN-gamma and PGE2 extends to downstream cytokine- and chemokine-release; PGE2 counters the effects of IFN-gamma, on the release of IP-10, IL-8, TNFalpha and IL-1beta. To gain further insight into IFN-gamma-mediated cellular events in rheumatoid arthritis, we assessed the effects of IFN-gamma on gene expression in fibroblast-like synoviocytes. We observed an IFN-gamma-dependent up-regulation of macrophage-attracting chemokines, and down-regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE2 and IFN-gamma which may represent a fundamental mechanism of immune control in diseases such as RA. For details, see Mathieu MC et al, EJI, issue 7, 2008
2008-05-29 | E-GEOD-11575 | biostudies-arrayexpress
Project description:Increasing evidence suggests that cyclooxygenase-2 (COX-2) is involved in synaptic transmission and plasticity, and prostaglandin E2 (PGE2) is a key molecule in COX-2-meduated synaptic modification. However, the precise mechanisms, in particular, which subtypes of PGE2 receptors (EPs) mediate the PGE2-induced synaptic response, are not clear. Recently, we demonstrated that EPs are expressed heterogeneously in the hippocampus, and EP2/4 are mainly expressed in presynaptic terminals. Here, we report that PGE2 increased synaptic stimulus-evoked amplitudes of EPSPs in hippocampal slices and frequency of miniature EPSCs (mEPSCs) in hippocampal neurons in culture. These actions were mimicked by an EP2 agonist and attenuated by protein kinase A inhibitors. Decrease of EP2 expression through silencing the EP2 gene eliminated PGE2-induced increase of the frequency of mEPSCs. COX-2 and microsomal PGE synthase-1 (mPGES-1) and mPGES-2 are present in postsynaptic dendritic spines, because they are colocalized with PSD-95 (postsynaptic density-95), a postsynaptic marker. In addition, the frequency of mEPSCs was enhanced in neurons pretreated with interleukin-1beta or lipopolysaccharide, which elevated expression of COX-2 and mPGES-1 and produced PGE2, and this enhancement was inhibited by a COX-2 inhibitor that inhibited production of PGE2. Our results suggest that PGE2 synthesized by postsynaptically localized COX-2 functions as a retrograde messenger in hippocampal synaptic signaling via a presynaptic EP2 receptor.
| S-EPMC6725559 | biostudies-literature
Project description:PGE2 is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE2, acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE2, we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes. Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependent inhibition of the expression of genes involved in the IFN-gamma activation pathway, including IFN-gamma itself. This effect of the PGE2/EP4 axis on IFN-gamma is a reciprocal phenomenon since IFN-gamma blocks PGE2 release and blocks EP receptor expression. The mutually antagonistic relationship between IFN-gamma and PGE2 extends to downstream cytokine- and chemokine-release; PGE2 counters the effects of IFN-gamma, on the release of IP-10, IL-8, TNFalpha and IL-1beta. To gain further insight into IFN-gamma-mediated cellular events in rheumatoid arthritis, we assessed the effects of IFN-gamma on gene expression in fibroblast-like synoviocytes. We observed an IFN-gamma-dependent up-regulation of macrophage-attracting chemokines, and down-regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE2 and IFN-gamma which may represent a fundamental mechanism of immune control in diseases such as RA.
2008-05-29 | GSE11575 | GEO
Project description:BMDMs were generated via differentiation of bone marrow cells in culture media containing m-CSF for 7 day. Upon differentiation, BMDMs were left untreated or stimulated with LPS, IFNa, PGE2, LPS+PGE2, or IFNa+PGE2.
2021-06-01 | E-MTAB-9253 | biostudies-arrayexpress
Project description:Prostaglandin E2 (PGE2) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE2 (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE2 markedly enhanced hTSC proliferation. The expression levels of stem cell marker genes, specifically SSEA-4 and Stro-1, were more extensive in hTSCs treated with low concentrations of PGE2 than in cells treated with high levels of PGE2. Moreover, high levels of PGE2 induced hTSCs to differentiate aberrantly into non-tenocytes, which was evident by the high levels of PPARγ, collagen type II, and osteocalcin expression in hTSCs treated with PGE2 at concentrations >1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo.
| S-EPMC3913640 | biostudies-literature
Project description:Tumour immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumours can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on NK cells to inhibit anti-tumour immunity. However, it is unclear precisely how PGE2 influences NK cell tumour-restraining functions. Here, we investigated how treatment with PGE2 over 24 hours affects gene expression in human NK cells.
2023-11-28 | E-MTAB-13106 | biostudies-arrayexpress