scholarly journals Amebic Infection in the Human Colon Induces Cyclooxygenase-2

2001 ◽  
Vol 69 (5) ◽  
pp. 3382-3388 ◽  
Author(s):  
William F. Stenson ◽  
Zhi Zhang ◽  
Terrence Riehl ◽  
Samuel L. Stanley
Keyword(s):  
Epithelial Cells ◽  
Severe Combined Immunodeficiency ◽  
Fold Increase ◽  
Neutrophil Infiltration ◽  
Human Colon ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Myeloperoxidase Activity ◽  
Epithelial Permeability ◽  
Cyclooxygenase 1

ABSTRACT We sought to determine if infection of the colon withEntamoeba histolytica induces the expression of cyclooxygenase-2 and, if it does, to determine the contribution of prostaglandins produced through cyclooxygenase-2 to the host response to amebic infection. Human fetal intestinal xenografts were implanted subcutaneously in mice with severe combined immunodeficiency and allowed to grow; the xenografts were then infected with E. histolytica trophozoites. Infection with E. histolytica resulted in the expression of cyclooxygenase-2 in epithelial cells and lamina propria macrophages. Infection with E. histolytica increased prostaglandin E2(PGE2) levels 10-fold in the xenografts and resulted in neutrophil infiltration, as manifested by an 18-fold increase in myeloperoxidase activity. Amebic infection also induced an 18-fold increase in interleukin 8 (IL-8) production and a >100-fold increase in epithelial permeability. Treatment of the host mouse with indomethacin, an inhibitor of cyclooxygenase-1 and cyclooxygenase-2, or with NS-398, a selective inhibitor of cyclooxygenase-2, resulted in (i) decreased PGE2 levels, (ii) a decrease in neutrophil infiltration, (iii) a decrease in IL-8 production, and (iv) a decrease in the enhanced epithelial permeability seen with amebic infection. These results indicate that amebic infection in the colon induces the expression of cyclooxygenase-2 in epithelial cells and macrophages. Moreover, prostaglandins produced through cyclooxygenase-2 participate in the mediation of the neutrophil response to infection and enhance epithelial permeability.

Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis

1997 ◽  
Vol 273 (1) ◽  
pp. G75-G82 ◽  
Author(s):  
S. Keates ◽  
A. C. Keates ◽  
E. Mizoguchi ◽  
A. Bhan ◽  
C. P. Kelly
Keyword(s):  
Ulcerative Colitis ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Primary Source ◽  
Fold Increase ◽  
Human Colon ◽  
Neutrophil Recruitment ◽  
Normal Colon ◽  
Necrosis Factor Alpha ◽  
Cytokine Stimulation

Epithelial cell-derived neutrophil-activating protein-78 (ENA-78) is a neutrophil-directed C-X-C chemokine. We report that Caco-2 and T84 human intestinal epithelial cells produce ENA-78 after stimulation by interleukin (IL)-1 beta or tumor necrosis factor-alpha. Caco-2 cells show increased IL-8 production at 4-12 h and increased ENA-78 production at 8-24 h after cytokine stimulation. Immunohistochemical studies in normal human colon and in ulcerative colitis demonstrate ENA-78 immunoreactivity principally associated with crypt epithelial cells. Furthermore, human colonic tissues from patients with ulcerative colitis show elevated levels of ENA-78 mRNA (24-fold increase, P < 0.01) and protein (4-fold increase, P < 0.05) compared with normal controls. Thus ENA-78 is produced in normal colon and in ulcerative colitis and is predominantly of enterocyte origin. The kinetics of ENA-78 induction in human colon epithelial cell lines are delayed and prolonged compared with IL-8. We propose that ENA-78 and IL-8 serve complementary and sequential roles in neutrophil recruitment in ulcerative colitis. ENA-78 as an enterocyte-derived, neutrophil-activating chemokine may be especially important in neutrophil recruitment from the lamina propria into the epithelial layer.

Meloxicam Inhibits Prostaglandin E2 Generation via Cyclooxygenase 2 in the Inflammatory Site but Not That via Cyclooxygenase 1 in the Stomach

Pharmacology ◽  
2000 ◽  
Vol 61 (4) ◽  
pp. 244-250 ◽  
Author(s):  
Keiko Ogino ◽  
Ko Hatanaka ◽  
Michiko Kawamura ◽  
Takashi Ohno ◽  
Yoshiteru Harada
Keyword(s):  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Cyclooxygenase 1 ◽  
Inflammatory Site

scholarly journals Despite Transcriptional and Functional Coordination, Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Largely Reside in Distinct Lipid Microdomains in WISH Epithelial Cells

2005 ◽  
Vol 53 (11) ◽  
pp. 1391-1401 ◽  
Author(s):  
William E. Ackerman IV ◽  
John M. Robinson ◽  
Douglas A. Kniss
Keyword(s):  
High Resolution ◽  
Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Potential Mechanism ◽  
Prostaglandin E Synthase ◽  
Lipid Microdomains ◽  
Cox 2 ◽  
Cytokine Stimulation ◽  
Soluble Fractions

Cytokine-induced prostaglandin (PG)E2 synthesis requires increased expression of cyclooxygenase-2 (COX-2) in human WISH epithelial cells. Recently, an inducible downstream PGE synthase (microsomal PGE synthase-1, mPGES-1) has been implicated in this inflammatory pathway. We evaluated cooperation between COX-2 and mPGES-1 as a potential mechanism for induced PGE2 production in WISH cells. Cytokine stimulation led to increased expression of both enzymes. Selective pharmacological inhibition of these enzymes demonstrated that induced PGE2 release occurred through a dominant COX-2/mPGES-1 pathway. Unexpectedly, immunofluorescent microscopy revealed that the expression of these enzymes was not tightly coordinated among cells after cytokine challenge. Within cells expressing high levels of both mPGES-1 and COX-2, immunolabeling of high-resolution semithin cryosections revealed that COX-2 and mPGES-1 were largely segregated to distinct regions within continuous intracellular membranes. Using biochemical means, it was further revealed that the majority of mPGES-1 resided within detergent-insoluble membrane fractions, whereas COX-2 was found only in detergent-soluble fractions. We conclude that although mPGES-1 and COX-2 show transcriptional and functional coordination in cytokine-induced PGE2 synthesis, complementary morphological and biochemical data suggest that a majority of intracellular mPGES-1 and COX-2 are segregated to discrete lipid microdomains in WISH epithelial cells.

scholarly journals gem-Difluorobisarylic derivatives: design, synthesis and anti-inflammatory effect

BMC Chemistry ◽  
2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Abeer J. Ayoub ◽  
Layal Hariss ◽  
Nehme El-Hachem ◽  
Ghewa A. El-Achkar ◽  
Sandra E. Ghayad ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Protein Expression ◽  
Interleukin 6 ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Diaryl Ethers ◽  
Cyclooxygenase 1 ◽  
Anti Inflammatory ◽  
Oxide Synthase

Abstract Introduction New fluorinated diaryl ethers and bisarylic ketones were designed and evaluated for their anti-inflammatory effects in primary macrophages. Methods The synthesis of the designed molecules started from easily accessible and versatile gem-difluoro propargylic derivatives. The desired aromatic systems were obtained using Diels–Alder/aromatization sequences and this was followed by Pd-catalyzed coupling reactions and, when required, final functionalization steps. Both direct inhibitory effects on cyclooxygenase-1 or -2 activities, protein expression of cyclooxygenase-2 and nitric oxide synthase-II and the production of prostaglandin E2, the pro-inflammatory nitric oxide and interleukin-6 were evaluated in primary murine bone marrow-derived macrophages in response to lipopolysaccharide. Docking of the designed molecules in cyclooxygenase-1 or -2 was performed. Results Only fluorinated compounds exerted anti-inflammatory activities by lowering the secretion of interleukin-6, nitric oxide, and prostaglandin E2, and decreasing the protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in mouse primary macrophages exposed to lipopolysaccharide, as well as cyclooxygenase activity for some inhibitors with different efficiencies depending on the R-groups. Docking observation suggested an inhibitory role of cyclooxygenase-1 or -2 for compounds A3, A4 and A5 in addition to their capacity to inhibit nitrite, interleukin-6, and nitric oxide synthase-II and cyclooxygenase-2 expression. Conclusion The new fluorinated diaryl ethers and bisarylic ketones have anti-inflammatory effects in macrophages. These fluorinated compounds have improved potential anti-inflammatory properties due to the fluorine residues in the bioactive molecules.

Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE2dependent through decreases in COX-2 and cPLA2protein levels

2006 ◽  
Vol 101 (4) ◽  
pp. 1127-1135 ◽  
Author(s):  
Mark J. Cowan ◽  
Timothy Coll ◽  
James H. Shelhamer
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Phospholipase A ◽  
Prostaglandin E ◽  
Airway Epithelial ◽  
Cyclooxygenase Inhibition ◽  
Protein Levels ◽  
Human Airway ◽  
Cytosolic Phospholipase

Both ornithine decarboxylase inhibition to deplete polyamines and cyclooxygenase inhibition diminish the migration response to injury of human airway epithelial cells in tissue culture monolayers by ∼75%. Restoration of normal migration responses is achieved in the polyamine depleted system either by exogenous reconstitution of polyamines or the addition of prostaglandin E2(PGE2). However, only PGE2was able to restore migration in the cyclooxygenase-inhibited systems. Western blot for cyclooxygenase-2 and cytosolic phospholipase A2protein levels and ELISAs for PGE2secretion demonstrate dramatic increases over 24–48 h after monolayer wounding. These increases are completely abolished by polyamine depletion or cyclooxygenase inhibition. We conclude that polyamine inhibition decreases cellular migration in response to injury in airway epithelial cells at least in part through inhibiting normal PGE2production in response to injury. This may be brought about by decreases in cytosolic phospholipase A2and cyclooxygenase-2 protein levels.

scholarly journals Relative contribution of cyclooxygenases, epoxyeicosatrienoic acids, and pH to the cerebral blood flow response to vibrissal stimulation

2012 ◽  
Vol 302 (5) ◽  
pp. H1075-H1085 ◽  
Author(s):  
Xiaoguang Liu ◽  
Chunyuan Li ◽  
John R. Falck ◽  
David R. Harder ◽  
Raymond C. Koehler
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabotropic Glutamate Receptors ◽  
Cyclooxygenase 2 ◽  
Model Systems ◽  
Epoxyeicosatrienoic Acids ◽  
Prostaglandin E ◽  
Cyclooxygenase 1 ◽  
Group I ◽  
Whisker Stimulation

The increase in cerebral blood flow (CBF) during neuronal activation can be only partially attenuated by individual inhibitors of epoxyeicosatrienoic acids (EETs), cyclooxgenase-2, group I metabotropic glutamate receptors (mGluR), neuronal nitric oxide synthase (nNOS), N-methyl-D-aspartate receptors, or adenosine receptors. Some studies that used a high concentration (500 μM) of the cyclooxygenase-1 inhibitor SC-560 have implicated cyclooxygenase-1 in gliovascular coupling in certain model systems in the mouse. Here, we found that increasing the concentration of SC-560 from 25 μM to 500 μM over whisker barrel cortex in anesthetized rats attenuated the CBF response to whisker stimulation. However, exogenous prostaglandin E2 restored the response in the presence of 500 μM SC-560 but not in the presence of a cyclooxygenase-2 inhibitor, thereby suggesting a limited permissive role for cyclooxygenase-1. Furthermore, inhibition of the CBF response to whisker stimulation by an EET antagonist persisted in the presence of SC-560 or a cyclooxygenase-2 inhibitor, thereby indicating that the EET-dependent component of vasodilation did not require cyclooxygenase-1 or -2 activity. With combined inhibition of cyclooxygenase-1 and -2, mGluR, nNOS, EETs, N-methyl-D-aspartate receptors, and adenosine 2B receptors, the CBF response was reduced by 60%. We postulated that the inability to completely block the CBF response was due to tissue acidosis resulting from impaired clearance of metabolically produced CO2. We tested this idea by increasing the concentration of superfused bicarbonate from 25 to 60 mM and found a markedly reduced CBF response to hypercapnia. However, increasing bicarbonate had no effect on the initial or steady-state CBF response to whisker stimulation with or without combined inhibition. We conclude that the residual response after inhibition of several known vasodilatory mechanisms is not due to acidosis arising from impaired CO2 clearance when the CBF response is reduced. An unidentified mechanism apparently is responsible for the rapid, residual cortical vasodilation during vibrissal stimulation.

scholarly journals FHIT suppresses inflammatory carcinogenic activity by inducing apoptosis in esophageal epithelial cells

2010 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
Koshi Mimori ◽  
Takehiko Yokobori ◽  
Masaaki Iwatsuki ◽  
Tomoya Sudo ◽  
Fumiaki Tanaka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Clinical Samples ◽  
Prostaglandin E ◽  
In Vivo Analysis ◽  
Esophageal Epithelial Cells ◽  
Vitro Analysis ◽  
In Vitro Analysis

We focused on the mechanism by which FHIT suppresses neoplastic transformation in normal but damaged esophageal epithelial cells exposed to inflammatory stimuli in vivo and to chemo-radiotherapy in clinical samples. For in vitro analysis, Adenoviral-FHIT (Ad-FHIT) in TE4 and TE2 were used for microarray analysis. For in vivo analysis, wild-type (WT) FHIT and FHIT-deficient (KO) C57BL/6 mice were exposed to N-nitrosomethylbenzylamine (NMBA) and to a cyclooxygenase-2 inhibitor (COXI). Considering DNA damage on clinical samples, expressions of FHIT, BAX and PCNA were evaluated by comparing between 3 cases of esophageal cancer cases of the chemo-radiotherapy responder and 7 cases of the non-responder. In in vitro analysis, we listed the down-regulated genes in Ad-FHIT that significantly control Lac-Z infected cells, such as prostaglandin E receptor 4, cyclooxygenase-1 and cyclooxygenase-2. In in vivo analysis, FHIT-KO mice were much more susceptible to tumorigenesis than were FHIT-WT mice. A significant difference in PGE2 activation was observed between FHIT-WT mice (5.2 ng/mL) and FHIT-KO mice (28.4 ng/mL) after exposure to NMBA in the absence of COXI as determined by ELISA assay (P less than 0.01). BAX expression was significantly higher in FHIT-WT (1.0±0.43) than in FHIT-KO (0.17±0.17) (P less than 0.05). The IHC score for FHIT and BAX expression was significantly higher in responders than the others (P less than 0.05). FHIT possesses tumor suppressor activity by induction of apoptosis in damaged cells after exposure to inflammatory carcinogens and DNA damaging chemo-radiotherapy.

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