scholarly journals The Induction of Cyclooxygenase-2 in IL-1β-Treated Endothelial Cells is Inhibited by Prostaglandin E2 through cAMP

1999 ◽  
Vol 8 (6) ◽  
pp. 287-294 ◽  
Author(s):  
Pravit Akarasereenont ◽  
Kitirat Techatrisak ◽  
Sirikul Chotewuttakorn ◽  
Athiwat Thaworn
Keyword(s):  
Endothelial Cells ◽  
Biological Activities ◽  
Umbilical Vein ◽  
The Body ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Negative Feedback Regulation ◽  
Cox 2 ◽  
Arachidonic Acids ◽  
Cox 1

Prostaglandins (PGS) have numerous cardiovascular and inflammatory effects. Cyclooxygenase (COX), which exists as COX-1 and COX-2 isoforms, is the first enzyme in the pathway in which arachidonic acid is converted to PGs. Prostaglandin E2 (PGE2) exerts a variety of biological activities for the maintenance of local homeostasis in the body. Elucidation of PGE2 involvement in the signalling molecules such as COX could lead to potential therapeutic interventions. Here, we have investigated the effects of PGE2 on the induction of COX-2 in human umbilical vein endothelial cells (HUVEC) treated with interleukin-1β (IL-1β 1 ng/ml). COX activity was measured by the production of 6-keto-PGF1α, PGE2, PGF2α and thromboxane B2 (TXB2) in the presence of exogenous arachidonic acids (10 μM for 10 min) using enzyme immunoassay (EIA). COX-1 and COX-2 protein was measured by immunoblotting using specific antibody. Untreated HUVEC contained only COX-1 protein while IL-1β treated HUVEC contained COX-1 and COX-2 protein. PGE2 (3 μM for 24 h) did not affect on COX activity and protein in untreated HUVEC. Interestingly, PGE2 (3 μM for 24 h) can inhibit COX-2 protein, but not COX-1 protein, expressed in HUVEC treated with IL1 β. This inhibition was reversed by coincubation with forskolin (100 μM). The increased COX activity in HUVEC treated with IL-1β was also inhibited by PGE2 (0.03, 0.3 and 3 μM for 24 h) in a dose-dependent manner. Similarly, forskolin (10, 50 or 100 μM) can also reverse the inhibition of PGE2 on increased COX activity in IL-1β treated HUVEC. The results suggested that (i) PGE2 can initiate negative feedback regulation in the induction of COX-2 elicited by IL-1β in endothelial cells, (ii) the inhibition of PGE2 on COX-2 protein and activity in IL-1β treated HUVEC is mediated by cAMP and (iii) the therapeutic use of PGE2 in the condition which COX-2 has been involved may have different roles.

scholarly journals Evaluation of Anti-Inflammatory Components of Guizhi Fuling Capsule, an Ancient Chinese Herbal Formula, in Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Yuzhong Zheng ◽  
Guizhong Xin ◽  
Guowei Gong ◽  
Tina TX Dong ◽  
Ping Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Active Components ◽  
Human Umbilical Vein ◽  
Cellular Inflammation ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Umbilical Vein Endothelial Cells ◽  
Cox 1

Background. Guizhi Fuling capsule (GFC), a well-known formula composed of five medicinal herbs, is commonly prescribed to treat primary dysmenorrhea, as well as to achieve good clinical efficacy in China. However, the active components of GFC have not been identified. Here, the anti-inflammatory functions of GFC, as well as its major ingredients, were evaluated in human umbilical vein endothelial cells (HUVECs). Methods. Lipopolysaccharide (LPS) was used in HUVECs to imitate the cellular inflammation. Then, GFC-triggered mRNA expressions of cyclooxygenase-1 (COX-1) and COX-2 were determined by real-time PCR, while the expression of COX-2 protein was revealed by western blotting. Besides, nine components of GFC were evaluated for their contribution value in the anti-dysmenorrhea effects Results. The application of GFC downregulated the mRNA expressions of COX-1 and COX-2 mRNAs. Nine major components of GFC were tested in the inflammatory system, and three compounds, including paeoniflorin, benzoylpaeoniflorin, and amygdalin, exhibited robust activation in HUVECs. The combination of paeoniflorin, benzoylpaeoniflorin, and amygdalin showed over 80% of the anti-inflammatory activation. Conclusion. Our study supports that GFC plays a promising role in anti-dysmenorrhea function by decreasing COXs’ expression. Besides, paeoniflorin, benzoylpaeoniflorin, and amygdalin could be considered as major regulators for the anti-dysmenorrhea effects of GFC.

Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through ATP-binding cassette transporter A1

2011 ◽  
Vol 301 (3) ◽  
pp. C739-C748 ◽  
Author(s):  
Donghui Liu ◽  
Liang Ji ◽  
Xunliang Tong ◽  
Bing Pan ◽  
Jing-Yan Han ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Cyclooxygenase 2 ◽  
Mitogen Activated Protein Kinase ◽  
Atp Binding ◽  
Dependent Manner ◽  
Atp Binding Cassette Transporter ◽  
Apolipoprotein A ◽  
Cox 2 ◽  
Atp Binding Cassette

High-density lipoprotein (HDL) can induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in endothelial cells to exert multiple antiatherogenic functions. This effect has been attributed mainly to the role of sphingosine-1-phosphate (S1P) integrated in HDL. However, whether apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, could induce COX-2 expression and PGI-2 release still remains unclear. In the present study, we selectively delipidated HDL and confirmed that apoA-I could facilitate COX-2 expression and PGI-2 production in human umbilical vein endothelial cells (HUVECs). ApoA-I, but not trypsinized apoA-I, induced COX-2 expression in a time- and dose-dependent manner consistent with a key role for apoA-I in this process. Additionally, cotreatment of apoA-I with S1P further enhanced COX-2 expression and PGI-2 production in HUVECs. These effects triggered by apoA-I were not inhibited by pertussis toxin, consistent with SIP receptor independent pathway for apoA-I effect. Moreover, we demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK), extracellular receptor kinase (ERK) 1/2, and JAK2 pathways by apoA-I was involved in the expression of COX-2 and the release of PGI-2 in HUVECs, and these effects were inhibited by their specific inhibitors, respectively. Small interfering RNA experiments showed that ATP binding-cassette transporter A1 (ABCA1) was required for COX-2 expression and PGI-2 release induced by apoA-I. Thus our results indicate that apoA-I induces COX-2 expression and PGI-2 release through ABCA1 and the activation of intracellular p38 MAPK, ERK1/2, as well as JAK2 pathways, and apoA-I can reinforce these effects with S1P in HUVECs. These novel effects of apoA-I could in part mediate antiatherogenic effects of HDL.

PGE2 reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop

2003 ◽  
Vol 284 (2) ◽  
pp. C302-C309 ◽  
Author(s):  
Lyne I. Lemieux ◽  
Sherine S. Rahal ◽  
Chris R. J. Kennedy
Keyword(s):  
Arachidonic Acid ◽  
Cell Line ◽  
Selective Inhibition ◽  
Renal Diseases ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Glomerular Function ◽  
Cox 2 ◽  
Regulatory Loop ◽  
Cox 1

Increased glomerular prostaglandin E2 (PGE2) production is associated with the progression of diseases such as membranous nephropathy, nephrotic syndrome, and anti-Thy1 nephritis. We investigated the signaling pathways that regulate the synthesis and actions of PGE2 in glomerular podocytes. To study its actions, we assessed the ability of PGE2 to regulate the production of its own precursor, arachidonic acid (AA), in a mouse podocyte cell line. PGE2 dose-dependently reduced phorbol ester (PMA)-mediated AA release. Inhibition of PMA-stimulated AA release by PGE2 was found to be cAMP/PKA-dependent, because PGE2 significantly increased levels of this second messenger, whereas the inhibitory actions of PGE2 were reversed by PKA inhibition and reproduced by the cAMP-elevating agents forskolin and IBMX. PGE2 synthesis in this podocyte cell line increased fourfold at 60 min in response to PMA, coinciding with upregulation of cyclooxygenase (COX)-2 but not COX-1 levels. However, PGE2 synthesis was significantly reduced by COX-1-selective inhibition, yet to a lesser extent by COX-2-selective inhibition. Our findings suggest that PMA-stimulated PGE2 synthesis in mouse podocytes requires both basal COX-1 activity and induced COX-2 expression, and that PGE2 reduces PMA-stimulated AA release in a cAMP/PKA-dependent manner. Such an autocrine regulatory loop might have important consequences for podocyte and glomerular function in the context of renal diseases involving PGE2 synthesis.

scholarly journals Vascular and Blood Compatibility of Engineered Cationic Cellulose Nanocrystals in Cell-Based Assays

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2072
Author(s):  
Alexandre Bernier ◽  
Tanner Tobias ◽  
Hoang Nguyen ◽  
Shreshth Kumar ◽  
Beza Tuga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Cellulose Nanocrystals ◽  
Blood Compatibility ◽  
Biological Activities ◽  
Umbilical Vein ◽  
Circulatory System ◽  
Dependent Manner ◽  
Umbilical Vein Endothelial Cells ◽  
The Impact

An emerging interest regarding nanoparticles (NPs) concerns their potential immunomodulatory and pro-inflammatory activities, as well as their impact in the circulatory system. These biological activities of NPs can be related to the intensity and type of the responses, which can raise concerns about adverse side effects and limit the biomedical applicability of these nanomaterials. Therefore, the purpose of this study was to investigate the impact of a library of cationic cellulose nanocrystals (CNCs) in the human blood and endothelial cells using cell-based assays. First, we evaluated whether the cationic CNCs would cause hemolysis and aggregation or alteration on the morphology of red blood cells (RBC). We observed that although these nanomaterials did not alter RBC morphology or cause aggregation, at 24 h exposure, a mild hemolysis was detected mainly with unmodified CNCs. Then, we analyzed the effect of various concentrations of CNCs on the cell viability of human umbilical vein endothelial cells (HUVECs) in a time-dependent manner. None of the cationic CNCs caused a dose-response decrease in the cell viability of HUVEC at 24 h or 48 h of exposure. The findings of this study, together with the immunomodulatory properties of these cationic CNCs previously published, support the development of engineered cationic CNCs for biomedical applications, in particular as vaccine nanoadjuvants.

Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells

2008 ◽  
Vol 295 (6) ◽  
pp. C1510-C1517 ◽  
Author(s):  
Hideyuki Yamawaki ◽  
Kazuaki Saito ◽  
Muneyoshi Okada ◽  
Yukio Hara
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Morphological Changes ◽  
Cell Damage ◽  
Umbilical Vein ◽  
P38 Map Kinase ◽  
Diabetic Patients ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cox 2

Methylglyoxal (MGO) is a reactive metabolite of glucose. Since the plasma concentration of MGO is increased in diabetic patients, MGO is implicated in diabetes-associated vascular endothelial cells (ECs) injury, which might be responsible for atherosclerosis. In the present study, we examined effects of treatment of human umbilical vein ECs with MGO on EC morphology and inflammatory responses. MGO (24 h) induced cytotoxic morphological changes in a concentration-dependent manner (0–420 μM). MGO induced mRNA and protein expression of cyclooxygenase (COX)-2 in a concentration (0–420 μM)- and time (6–24 h)-dependent manner. COX-2 induction was associated with increased PGE2 release. Acute treatment with MGO (20 min) induced concentration-dependent (0–420 μM) activation of JNK and p38 MAP kinase but not ERK or NF-κB. Both the JNK inhibitor SP600125 and the p38 inhibitor SB203580 prevented the MGO induction of COX-2. However, inhibiting JNK and p38 or COX-2 was ineffective to the morphological damage by MGO (420 μM, 24 h). EUK134, a synthetic combined superoxide dismutase/catalase mimetic, had no effect on MGO-induced COX-2. Present results indicated that MGO mediates JNK- and p38-dependent EC inflammatory responses, which might be independent of oxidative stress. On the other hand, MGO-induced morphological cell damage seems unlikely to be associated with COX-2-PGE2.

Regulation of PGE2and PGI2release from human umbilical vein endothelial cells by actin cytoskeleton

2001 ◽  
Vol 281 (3) ◽  
pp. C1038-C1045 ◽  
Author(s):  
Sara J. Sawyer ◽  
Suzanne M. Norvell ◽  
Suzanne M. Ponik ◽  
Fredrick M. Pavalko
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Fold Increase ◽  
Prostaglandin E ◽  
Microtubule Network ◽  
Human Umbilical Vein ◽  
Drug Treatments ◽  
Cox 2 ◽  
Umbilical Vein Endothelial Cells

Disruption of microfilaments in human umbilical vein endothelial cells (HUVEC) with cytochalasin D (cytD) or latrunculin A (latA) resulted in a 3.3- to 5.7-fold increase in total synthesis of prostaglandin E2(PGE2) and a 3.4- to 6.5-fold increase in prostacyclin (PGI2) compared with control cells. Disruption of the microtubule network with nocodazole or colchicine increased synthesis of PGE21.7- to 1.9-fold and PGI21.9- to 2.0-fold compared with control cells. Interestingly, however, increased release of PGE2and PGI2from HUVEC into the media occurred only when microfilaments were disrupted. CytD treatment resulted in 6.7-fold more PGE2and 3.8-fold more PGI2released from HUVEC compared with control cells; latA treatment resulted in 17.7-fold more PGE2and 11.2-fold more PGI2released compared with control cells. Both increased synthesis and release of prostaglandins in response to all drug treatments were completely inhibited by NS-398, a specific inhibitor of cyclooxygenase-2 (COX-2). Disruption of either microfilaments using cytD or latA or of microtubules using nocodazole or colchicine resulted in a significant increase in COX-2 protein levels, suggesting that the increased synthesis of prostaglandins in response to drug treatments may result from increased activity of COX-2. These results, together with studies demonstrating a vasoprotective role for prostaglandins, suggest that the cytoskeleton plays an important role in maintenance of endothelial barrier function by regulating prostaglandin synthesis and release from HUVEC.

Posttranslational regulation of cyclooxygenase by tyrosine phosphorylation in cerebral endothelial cells

1998 ◽  
Vol 274 (1) ◽  
pp. C72-C81 ◽  
Author(s):  
Helena Parfenova ◽  
Liliya Balabanova ◽  
Charles W. Leffler
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Phosphorylation ◽  
Umbilical Vein ◽  
Vascular Cells ◽  
Protein Synthesis Inhibitors ◽  
Cerebral Microvessels ◽  
Protein Tyrosine ◽  
Newborn Pigs ◽  
Cox 2 ◽  
Cox 1

Endothelium-derived cyclooxygenase (COX) products regulate cerebral vascular tone in newborn pigs. Both COX-1 and COX-2 are constitutively expressed in endothelial cells from newborn pig cerebral microvessels. We investigated the role of protein phosphorylation in the regulation of COX activity. The protein tyrosine phosphatase (PTP) inhibitors phenylarsine oxide, vanadate, and benzylphosphonic acid rapidly stimulated COX activity, whereas the protein tyrosine kinase inhibitors, genistein and tyrphostins, inhibited it. Protein synthesis inhibitors did not reverse the stimulation of COX activity evoked by PTP inhibitors. Similar changes were observed in other vascular cells from newborn pigs that also express COX-1 and COX-2 (cerebral microvascular smooth muscle cells and aortic endothelial cells) but not in human umbilical vein endothelial cells or Swiss 3T3 fibroblasts that express COX-1 only. Tyrosine-phosphorylated proteins were immunodetected in endothelial cell lysates. COX-2 immunoprecipitated from32P-loaded endothelial cells incorporated32P that was increased by PTP inhibitors. COX-2, but not COX-1, was detected in endothelial fractions immunoprecipitated with anti-phosphotyrosine. These data indicate that tyrosine phosphorylation posttranslationally regulates COX activity in newborn pig vascular cells and that COX-2 is a substrate for phosphorylation.

Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells

2001 ◽  
Vol 281 (1) ◽  
pp. C166-C178 ◽  
Author(s):  
Helena Parfenova ◽  
Vladimir N. Parfenov ◽  
Boris V. Shlopov ◽  
Vladimir Levine ◽  
Sheryl Falkos ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nuclear Envelope ◽  
Nuclear Localization ◽  
Spatial Organization ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Cerebral Microvessels ◽  
Expression Activity ◽  
Cox 2 ◽  
Cox 1

We investigated the relationships among expression, activity, and spatial organization of cyclooxygenase (COX-1 and COX-2) in endothelial cells from porcine and human cerebral microvessels and from human umbilical vein. In quiescent cells, COX-1 was detected in the perinuclear zone and the cytoplasm, while COX-2 was mainly a nuclear resident possibly connected with the nuclear matrix. COX-2 immunogold labeling was situated in the nuclear envelope, at the nuclear pores, and in connection with the perichromatin regions of the nucleus, considered to be the sites of active transcription. In human endothelial cells transcriptionally activated by interleukin (IL)-1β, the nucleus remained a major COX-2 localization site during the first 12 h of stimulation, when COX-2 expression was maximally induced. The continuous rise in prostanoid synthesis at 17–23 h of stimulation was associated with COX-2 relocation from the nucleus to the nuclear envelope and the cytoplasm. IL-1β did not affect COX-1 expression, activity, and localization. COX-2 nuclear localization sites and trafficking between the nucleus and the cytoplasm in endothelial cells may indicate a novel function of COX-2 in regulating gene expression.

Comparative Study of Vanadate- and Phorbol Ester-induced Cyclo-oxygenase-2 Expression in Human Endothelial Cells

1999 ◽  
Vol 82 (11) ◽  
pp. 1545-1561 ◽  
Author(s):  
Kenzo Hirai ◽  
Yasuharu Ezumi ◽  
Eisuke Nishida ◽  
Takashi Uchiyama ◽  
Hiroshi Takayama
Keyword(s):  
Endothelial Cells ◽  
Protein Tyrosine Kinase ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Protein Tyrosine Phosphatases ◽  
Dependent Manner ◽  
Protein Tyrosine ◽  
Amino Terminal ◽  
Cox 2 ◽  
Umbilical Vein Endothelial Cells

SummaryOur previous study showed that vanadate, an inhibitor of protein tyrosine phosphatases, induced the expression of cyclo-oxygenase (COX)-2 in a protein-tyrosine-kinase (PTK)-dependent manner in human umbilical vein endothelial cells (HUVEC). Here, we further compared the actions of vanadate and phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), on induction of COX-2 with special reference to mitogen-activated protein kinases (MAPKs) in HUVEC. Vanadate induced activation of three families of MAPKs, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun amino-terminal kinase (JNK) 1, while activation of ERK1/2 alone was induced by PMA. The former activation by vanadate and the latter one by PMA were inhibited by tyrphostin-47, an inhibitor of PTKs, and by Ro31-8220, a PKC inhibitor, respectively. Either tyrphostin-47, PD98059, a specific inhibitor of the upstream kinase toward ERK1/2, or SB203580, a specific inhibitor of p38, completely suppressed vanadate-induction of COX-2 mRNA and protein. On the other hand, PMA-induction of COX-2 mRNA and protein was abolished by Ro31-8220 or PD98059 but not by SB203580. These data indicate that PMA-induced and PKC-dependent expression of COX-2 requires mainly activation of ERK1/2 among MAPKs, while activation of both ERK1/2 and p38 or possibly of all three families of MAPKs is necessary for vanadate-induced and PTK-dependent expression of COX-2.

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