scholarly journals The Cytotoxic Enterotoxin of Aeromonas hydrophila Induces Proinflammatory Cytokine Production and Activates Arachidonic Acid Metabolism in Macrophages

2000 ◽  
Vol 68 (5) ◽  
pp. 2808-2818 ◽  
Author(s):  
A. K. Chopra ◽  
X.-J. Xu ◽  
D. Ribardo ◽  
M. Gonzalez ◽  
K. Kuhl ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Proinflammatory Cytokines ◽  
Aeromonas Hydrophila ◽  
Tissue Injury ◽  
Biological Activities ◽  
Prostaglandin E ◽  
Intestinal Loop ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Cox 2

ABSTRACT An aerolysin-related cytotoxic enterotoxin (Act) of Aeromonas hydrophila possesses multiple biological activities, which include its ability to lyse red blood cells, destroy tissue culture cell lines, evoke a fluid secretory response in ligated intestinal loop models, and induce lethality in mice. The role of Act in the virulence of the organism has been demonstrated. In this study, we evaluated the potential of Act to induce production of proinflammatory cytokines associated with Act-induced tissue injury and Act's capacity to activate in macrophages arachidonic acid (AA) metabolism that leads to production of eicosanoids (e.g., prostaglandin E2[PGE2]). Our data indicated that Act stimulated the production of tumor necrosis factor alpha and upregulated the expression of genes encoding interleukin-1β (IL-1β) and IL-6 in the murine macrophage cell line RAW264.7. Act also activated transcription of the gene encoding inducible nitric oxide synthase. Act evoked the production of PGE2 coupled to the cyclooxygenase-2 (COX-2) pathway. AA is a substrate for PGE2, and Act produced AA from phospholipids by inducing group V secretory phospholipase A2. We also demonstrated that Act increased cyclic AMP (cAMP) production in macrophages. cAMP, along with PGE2, could potentiate fluid secretion in animal models because of infiltration and activation of macrophages resulting from Act-induced tissue injury. After Act treatment of RAW cells, we detected an increased translocation of NF-κB and cAMP-responsive element binding protein (CREB) to the nucleus using gel shift assays. Act also upregulated production of antiapoptotic protein Bcl-2 in macrophages, suggesting a protective role for Bcl-2 against cell death induced by proinflammatory cytokines. The increased expression of genes encoding the proinflammatory cytokines, COX-2, and Bcl-2 appeared correlated with the activation of NF-κB and CREB. This is the first report of the detailed mechanisms of action of Act from A. hydrophila.

scholarly journals Cyclophilin a as a Mediator of Tissue Injure and Nephrotoxicity

2012 ◽  
Vol 4 (2) ◽  
pp. 42-44
Author(s):  
Grace Moscoso-Solorzano ◽  
Gianna Mastroianni-Kirsztajn
Keyword(s):  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Cyclophilin A ◽  
Common Mechanism ◽  
Ppiase Activity ◽  
Expression Of Genes ◽  
Inflammatory Stimuli ◽  
Genes Encoding ◽  
Inflammatory Processes

Cyclophilin A (CypA) belongs to the peptidyl-prolil isomerase (PPlase) family of proteins and it is also known as the cellular receptor for cyclosporine A (CsA). CsA binds to CypA and inhibits the PPIase activity, but the CypA-CsA complex also binds to calcineurin that promotes the expression of genes encoding cytokines and other proteins required for immune response. In addition, the polymorphism variation of CypA promoter seems to have an influence on the expression of CypA in in vitro studies. CypA was also implicated in inflammatory processes (such as, among others, those observed in rheumatoid arthritis, atherosclerotic disease, nephrotoxicity) and it can be secreted by cells in response to inflammatory stimuli. CypA can also have a role in the molecular mechanisms by which CsA induces nephroxicity but these remain poorly understood. Recent studies suggest that CsA inhibition of CypA PPlase activity is a possible mechanism of this drug toxicity. In addition, CypA overexpression could be protective against CsA nephrotoxicity. Finally, the putative common mechanism by which CypA could be involved in CsA nephrotoxicity and tissue injury is related to its proinflammatory effects in cells.

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 Orostachys japonicusInhibits Expression of the TLR4, NOD2, iNOS, and COX-2 Genes in LPS-Stimulated Human PMA-Differentiated THP-1 Cells by Inhibiting NF-κB and MAPK Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yeo-Kwang Yoon ◽  
Hong-Jung Woo ◽  
Youngchul Kim
Keyword(s):  
Mapk Signaling ◽  
Mrna Levels ◽  
Inflammatory Agent ◽  
Expression Of Genes ◽  
Erk Phosphorylation ◽  
Genes Encoding ◽  
Pathogen Recognition Receptors ◽  
Cox 2 ◽  
High Concentrations ◽  
Proinflammatory Factors

Orostachys japonicusis traditionally used as an inflammatory agent. In this report, we investigated the effects ofO. japonicusextract on the expression of genes encoding pathogen-recognition receptors (TLR2, TLR4, NOD1, and NOD2) and proinflammatory factors (iNOS, COX-2, and cytokines) in LPS-stimulated PMA-differentiated THP-1 cells and the NF-κB and MAPK pathways.O. japonicusinduced toxicity at high concentrations but had no effect at concentrations lower than 25 μg/mL.O. japonicusinhibited LPS-induced TLR4 and NOD2 mRNA levels, suppressed LPS-induced iNOS and COX-2 transcription and translocation, and downregulated LPS-induced proinflammatory cytokine (IL-1β, IL-6, IL-8, and TNF-α) mRNA levels. In addition,O. japonicusinhibited LPS-induced NF-κB activation and IκBαdegradation and suppressed LPS-induced JNK, p38 MAPK, and ERK phosphorylation. Overall, our results demonstrate that the anti-inflammatory effects ofO. japonicusare mediated by suppression of NF-κB and MAPK signaling, resulting in reduced TLR4, NOD2, iNOS, and COX-2 expression and inhibition of inflammatory cytokine expression.

11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E2 in Rat Monocytes Stimulated with Lipopolysaccharide

2003 ◽  
Vol 228 (7) ◽  
pp. 786-794 ◽  
Author(s):  
Wieslaw Kozak ◽  
David M. Aronoff ◽  
Olivier Boutaud ◽  
Anna Kozak
Keyword(s):  
Cell Culture ◽  
Arachidonic Acid ◽  
Negative Feedback ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Epoxyeicosatrienoic Acid ◽  
Concentration Dependent Manner ◽  
Cox 2 ◽  
Cytochrome P 450

Cytochrome P-450 monooxygenase (epoxygenase)-derived arachidonic acid (AA) metabolites, including 11,12-epoxyeicosatrienoic acid (11,12-EET), possess anti-inflammatory and antipyretic properties. Prostaglandin E2 (PGE2), a cyclooxygenase (COX)-derived metabolite of AA, is a well-defined mediator of fever and inflammation. We have tested the hypothesis that 11,12-EET attenuates synthesis of PGE2 in monocytes, which are the cells that are indispensable for induction of fever and initiation of inflammation. Monocytes isolated from freshly collected rat blood were stimulated with lipopolysaccharide (LPS; 100 ng/2 × 105 cells) to induce COX-2 and stimulate generation of PGE2. SKF-525A, an inhibitor of epoxygenases, significantly augmented the lipopolysaccharide-provoked synthesis of PGE2 in cell culture in a concentration-dependent manner. It did not affect, however, elevation of the expression of COX-2 protein in monocytes stimulated with LPS. 11,12-EET also did not affect the induction of COX-2 in monocytes incubated with lipopolysaccharide. However, 11,12-EET suppressed, in a concentration-dependent fashion, the generation of PGE2 in incubates. Preincubation of a murine COX-2 preparation for 0–5 min with three concentrations of 11,12-EET (1, 5, and 10 μM) inhibited the oxygenation of [14C]-labeled AA by the enzyme. The inhibitory effect of 11,12-EET on COX-2 was time-and-concentration-dependent, suggesting a mechanism-based inhibition. Based on these data, we conclude that 11,12-EET suppresses generation of PGE2 in monocytes via modulating the activity of COX-2. These data support the hypothesis that epoxygenasederived AA metabolites constitute a negative feedback on the enhanced synthesis of prostaglandins upon inflammation.

The inhibitory effect of celecoxib on mouse hepatoma H22 cell line on the arachidonic acid metabolic pathwayThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 603-609 ◽  
Author(s):  
Zhigang Xu ◽  
Ming Zhang ◽  
Xiaoyan Lv ◽  
Dan Xiang ◽  
Xuewen Zhang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Peer Review Process ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Important Indicator ◽  
Protein Levels ◽  
Mouse Hepatoma ◽  
Cox 2 ◽  
Risk Of Cancer

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2). It may reduce the risk of cancer formation by affecting the metabolism of arachidonic acid (AA), which has been implicated in the development of cancer. Accordingly, this study was designed to determine the effects of celecoxib on the AA pathway in mouse hepatoma H22 cells. Celecoxib was found to inhibit the proliferation of H22 cells in a dose- and time-dependent manner. Low doses (50 and 100 µmol·L–1) of celecoxib caused an increase in the expression of cytosolic phospholipase A2 (cPLA2), but did not affect the expression of COX-2 in terms of the mRNA and protein levels. Surprisingly, the amount of AA was elevated and the level of prostaglandin E2 (PGE2) was unaltered in the culture supernatant. At higher celecoxib doses (200 and 400 µmol·L–1), the mRNA and protein of both COX-2 and cPLA2 were inhibited. The concentration of AA was increased, and PGE2 level was depressed in H22 cells. The ratio of AA to PGE2 was increased in a dose-dependent manner. Our findings suggest that the imbalance between AA and PGE2, characterized by increased AA at a low dosage and decreased PGE2 at a high dosage of celecoxib, was an important indicator of cytotoxicity of celecoxib on H22 cells.

scholarly journals Cyclooxygenases and prostaglandin E synthases in the endometrium of the rhesus monkey during the menstrual cycle

Reproduction ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 465-473 ◽  
Author(s):  
Tong Sun ◽  
Shi-Jie Li ◽  
Hong-Lu Diao ◽  
Chun-Bo Teng ◽  
Hong-Bin Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Menstrual Cycle ◽  
Rhesus Monkey ◽  
Luteal Phase ◽  
Glandular Epithelium ◽  
Prostaglandin E ◽  
Luminal Epithelium ◽  
Cox 2 ◽  
Rate Limiting ◽  
Cox 1

Cyclooxygenase (COX), a rate-limiting enzyme that produces prostaglandins (PGs) from arachidonic acid, exists in two isoforms, COX-1 and COX-2. PGE2 synthase (PGES) is a terminal prostanoid synthase and can enzymatically convert the cyclooxygenase product PGH2 to PGE2, including two isoforms: microsomal PGES (mPGES) and cytosolic PGES (cPGES). cPGES is predominantly linked with COX-1 to promote the immediate response. mPGES is preferentially coupled with the inducible COX-2 to promote delayed PGE2 generation. COX-2-deficient female mice are infertile with abnormalities in ovulation, fertilization, implantation and decidualization. The aim of this study was to examine immunohistochemically the expression pattern of COX-1, COX-2, mPGES and cPGES proteins in the endometrium of the rhesus monkey during the menstrual cycle. COX-1 immunostaining was mainly localized in the luminal epithelium and glandular epithelium near the lumen, and detected in all the stages during the menstrual cycle. COX-2 immunostaining was mainly localized in the luminal and glandular epithelium, and strongly shown during the mid-luteal phase (days 16 and 20) of the menstrual cycle. There was a strong cPGES immunostaining in the luminal and glandular epithelium on days 12, 16, 20 and 25 of the menstrual cycle. mPGES immunostaining was strongly detected in the glandular epithelium on days 20 and 25 of the menstrual cycle. These data suggest that the coupling of cPGES and COX-1 in the luminal epithelium may be responsible for the synthesis of PGE2 in monkey endometrium, and the coupling of mPGES and COX-2 in the glandular epithelium may be of importance for preparing the receptive endometrium.

scholarly journals The protective effects of 18β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway

2018 ◽  
Vol 16 ◽  
pp. 205873921876299 ◽  
Author(s):  
Donghui Cao ◽  
Jing Jiang ◽  
Dan Zhao ◽  
Menghui Wu ◽  
Houjun Zhang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Glycyrrhetinic Acid ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Acid Pathway ◽  
Ep2 Receptor ◽  
Arachidonic Acid Pathway

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for gastrointestinal diseases. Glycyrrhiza glabra, a traditional Chinese medicine, has been shown to safely suppress gastric cancer; however, the anti-inflammatory mechanisms in gastric tumorigenesis have been poorly investigated. Therefore, this study is committed to demonstrate the in vivo anti-inflammatory effect of 18β-glycyrrhetinic acid (GRA), the main active component of G. glabra. The lymphocytes and macrophages were heavily infiltrated in the transgenic mice that highly expressed cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1; however, a significant reduction was observed after treatment with GRA. In addition, GRA downregulated the protein levels of COX-2, GαS, EP2, and β-catenin, which were involved in the arachidonic acid pathway. In conclusion, our study showed the potential protective effects of GRA against inflammatory environment that might be involved in gastric tumorigenesis in vivo through the PGE2-EP2 receptor-mediated arachidonic acid pathway.

scholarly journals Effect of Acute and Prolonged Inflammation on the Gene Expression of Proinflammatory Cytokines and Their Receptors in the Anterior Pituitary Gland of Ewes

2020 ◽  
Vol 21 (18) ◽  
pp. 6939
Author(s):  
Karolina Wojtulewicz ◽  
Agata Krawczyńska ◽  
Dorota Tomaszewska-Zaremba ◽  
Maciej Wójcik ◽  
Andrzej P. Herman
Keyword(s):  
Gene Expression ◽  
Proinflammatory Cytokines ◽  
Anterior Pituitary ◽  
Acute Inflammation ◽  
Single Injection ◽  
Secretory Activity ◽  
External Jugular Vein ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Reproduction Process

An acute and prolonged inflammation inhibits the reproduction process by the disruption of the neurohormonal activity of the hypothalamic-pituitary-gonadal axis. It is thought that these changes may be caused by proinflammatory cytokines, i.e., interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) α. The aim of this study was to determine the effect of an acute and prolonged inflammation on the expression of genes encoding cytokine and their receptors, gonadotropin releasing hormone receptor (GnRHR), beta subunits of luteinizing hormone (LHβ) and follicle-stimulating (FSHβ) in the anterior pituitary (AP). Moreover, the circulating concentration of LH and FSH was also assayed. Two experiments were carried out on adult ewes which were divided into two control groups and treated with lipopolysaccharide (LPS; 400 ng / kg). Acute inflammation was caused by a single injection of LPS into the external jugular vein, while the chronic inflammation was induced by seven times LPS injection (one a day). In both experiments, animals were euthanized 3h after the last LPS / NaCl injection and the blood samples collected 15 min before euthanasia. An acute inflammation stimulates the expression of the IL-1β, IL-6 and TNFα genes and their receptors in the AP of sheep. Prolonged inflammation increased TNFα gene expression and both types of TNFα and IL-6 receptors. Both an acute and prolonged inflammation inhibited LHβ gene expression in the AP and reduced LH level in blood. A sevenfold LPS injection raises FSH concentration. The gene expression of GnRHR was reduced in the ovine AP only after a single injection of endotoxin. Our results suggest that there are important differences in the way how an acute and prolonged inflammation influence proinflammatory cytokines and their receptors gene expression in the AP of anestrous ewes, which could be reflected by differences in the AP secretory activity during these states.

scholarly journals Reactive Oxygen Species Mediated Prostaglandin E2 Contributes to Acute Response of Epithelial Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Ping Hu ◽  
Yin-Bo Peng ◽  
Yi-Fan Zhang ◽  
Ying Wang ◽  
Wei-Rong Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tissue Injury ◽  
Reactive Oxygen ◽  
Human Keratinocytes ◽  
Mechanical Injury ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Cox 2

Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase.

The expression of genes encoding for COX-2, MPO, iNOS, and sPLA2-IIA in patients with recurrent depressive disorder

2012 ◽  
Vol 138 (3) ◽  
pp. 360-366 ◽  
Author(s):  
Piotr Gałecki ◽  
Elżbieta Gałecka ◽  
Michael Maes ◽  
Marcelina Chamielec ◽  
Agata Orzechowska ◽  
...  
Keyword(s):  
Depressive Disorder ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Cox 2
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