Dexamethasone inhibits prostaglandin release from rabbit coronary microvessel endothelium

1986 ◽  
Vol 250 (6) ◽  
pp. C970-C977 ◽  
Author(s):  
R. M. Rosenbaum ◽  
C. D. Cheli ◽  
M. E. Gerritsen
Keyword(s):  
Endothelial Cell ◽  
Culture Media ◽  
Conditioned Media ◽  
Microvascular Endothelial Cell ◽  
Dexamethasone Treatment ◽  
Stimulatory Action ◽  
Prostaglandin Release ◽  
Cell Release ◽  
Microvascular Endothelial

The effects of dexamethasone on prostaglandin secretion by cultivated rabbit coronary microvascular endothelial (RCME) cells were investigated. Incubation of RCME cells with dexamethasone resulted in a time- and concentration-dependent decrease in prostaglandin accumulation in the culture media and reduced basal and A23187-stimulated prostaglandin (PG) E2 and 6-keto-PGF1 alpha release. The maximal effects of dexamethasone (50-80% inhibition) were achieved after 16-18 h of incubation with the steroid at a final concentration of 10(-7) M. The effects of dexamethasone treatment were partially reversed 24 h after removal of the steroid from the culture media. Dexamethasone treatment did not reduce arachidonic acid-stimulated prostaglandin synthesis, indicating that the level of inhibition was proximal to that of cyclooxygenase. The inhibitory effects of dexamethasone could be prevented by pretreatment of the RCME cells with actinomycin D or cycloheximide, suggesting a requirement for protein synthesis in the inhibitory action of dexamethasone. Conditioned media from dexamethasone-treated cells contained a factor that inhibited porcine pancreatic phospholipase A2 (PLA2) in vitro. Transfer of conditioned media from dexamethasone-treated cells to untreated cells did not reduce basal or stimulated prostaglandin release; in contrast, a stimulatory action was consistently observed. Adherence of rabbit peripheral polymorphonuclear leukocytes (PMN) to RCME cells was reduced when the leukocytes were pretreated with 10(-7) M dexamethasone (4 h). However, dexamethasone pretreatment of the RCME cells did not significantly effect granulocyte adhesion. Thus coronary microvascular endothelial cell prostaglandin production is regulated by glucocorticoids, and glucocorticoid-pretreated microvascular endothelial cell release an inhibitor of PLA2 activity into the culture media.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glycosaminoglycan Regulation by VEGFA and VEGFC of the Glomerular Microvascular Endothelial Cell Glycocalyx in Vitro

2013 ◽  
Vol 183 (2) ◽  
pp. 604-616 ◽  
Author(s):  
Rebecca R. Foster ◽  
Lynne Armstrong ◽  
Siân Baker ◽  
Dickson W.L. Wong ◽  
Emma C. Wylie ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelial

scholarly journals Methylglyoxal Impairs Brain Microvascular Endothelial Cell Function In Vivo and In Vitro

2009 ◽  
Vol 96 (3) ◽  
pp. 682a
Author(s):  
Aydin Tay ◽  
William G. Mayhan ◽  
Denise Arrick ◽  
Chun-Hong Shao ◽  
Hong Sun ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Microvascular Endothelial Cell ◽  
Brain Microvascular Endothelial Cell ◽  
Endothelial Cell Function ◽  
Microvascular Endothelial

scholarly journals Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

2021 ◽  
Author(s):  
Elina Korpela ◽  
Darren Yohan ◽  
Lee CL Chin ◽  
Anthony Kim ◽  
Xiaoyong Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Ionizing Radiation ◽  
Radiation Damage ◽  
Microvascular Endothelial Cell ◽  
Skin Damage ◽  
Cancer Radiotherapy ◽  
Microvascular Endothelial ◽  
Angiopoietin 1

Background Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients’ quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model. Methods Athymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons. Results In vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell density in wound granulation tissue. In vitro, Vasculotide enhanced the survival and function of irradiated endothelial cells. Conclusions Vasculotide administration reduces acute skin radiation damage in mice, and may do so by affecting several biological processes. This radiation protection approach may have clinical impact for cancer radiotherapy patients by reducing the severity of their acute skin radiation damage.

scholarly journals Bovine Organospecific Microvascular Endothelial Cell Lines as New and Relevant In Vitro Models to Study Viral Infections

2020 ◽  
Vol 21 (15) ◽  
pp. 5249 ◽  
Author(s):  
Anne-Claire Lagrée ◽  
Fabienne Fasani ◽  
Clotilde Rouxel ◽  
Marine Pivet ◽  
Marie Pourcelot ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Lines ◽  
T Antigen ◽  
In Vitro Studies ◽  
Microvascular Endothelial Cell ◽  
Target Cells ◽  
Microvascular Endothelial

Microvascular endothelial cells constitute potential targets for exogenous microorganisms, in particular for vector-borne pathogens. Their phenotypic and functional variations according to the organs they are coming from provide an explanation of the organ selectivity expressed in vivo by pathogens. In order to make available relevant tools for in vitro studies of infection mechanisms, our aim was to immortalize bovine organospecific endothelial cells but also to assess their permissivity to viral infection. Using transfection with SV40 large T antigen, six bovine microvascular endothelial cell lines from various organs and one macrovascular cell line from an umbilical cord were established. They display their own panel of endothelial progenitor/mature markers, as assessed by flow cytometry and RT-qPCR, as well as the typical angiogenesis capacity. Using both Bluetongue and foot-and-mouth disease viruses, we demonstrate that some cell lines are preferentially infected. In addition, they can be transfected and are able to express viral proteins such as BTV8-NS3. Such microvascular endothelial cell lines bring innovative tools for in vitro studies of infection by viruses or bacteria, allowing for the study of host-pathogen interaction mechanisms with the actual in vivo target cells. They are also suitable for applications linked to microvascularization, such as anti-angiogenic and anti-tumor research, growing fields in veterinary medicine.

scholarly journals Establishment and Characterization of Human Peripheral Nerve Microvascular Endothelial Cell Lines: A New in vitro Blood-Nerve Barrier (BNB) Model

2012 ◽  
Vol 37 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Masaaki Abe ◽  
Yasuteru Sano ◽  
Toshihiko Maeda ◽  
Fumitaka Shimizu ◽  
Yoko Kashiwamura ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Peripheral Nerve ◽  
Cell Lines ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelial

HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation

2005 ◽  
Vol 289 (2) ◽  
pp. H542-H548 ◽  
Author(s):  
Ramzi Ockaili ◽  
Ramesh Natarajan ◽  
Fadi Salloum ◽  
Bernard J. Fisher ◽  
Drew Jones ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Line ◽  
Heme Oxygenase ◽  
Ischemia Reperfusion ◽  
Microvascular Endothelial Cell ◽  
Endothelial Cell Line ◽  
Human Microvascular Endothelial Cell ◽  
Microvascular Endothelial

The CXC chemokine IL-8, which promotes adhesion, activation, and transmigration of polymorphonuclear neutrophils (PMN), has been associated with production of tissue injury in reperfused myocardium. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric peptide that is a key regulator of genes such as heme oxygenase (HO)-1 expressed under hypoxic conditions. We hypothesized that HO-1 plays an important role in regulating proinflammatory mediator production under conditions of ischemia-reperfusion. HIF-1 was activated in the human microvascular endothelial cell line (HMEC-1) with the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). DMOG significantly attenuated cytokine-induced IL-8 promoter activity and protein secretion and cytokine-induced PMN migration across human microvascular endothelial cell line HMEC-1 monolayers. In vivo studies in a rabbit model of myocardial ischemia-reperfusion showed that rabbits pretreated with a 20 mg/kg DMOG infusion ( n = 6) 24 h before study exhibited a 21.58 ± 1.76% infarct size compared with 35.25 ± 2.06% in saline-treated ischemia-reperfusion animals ( n = 6, change in reduction = 39%; P < 0.001). In DMOG-pretreated (20 mg/kg) animals, plasma IL-8 levels at 3 h after onset of reperfusion were 405 ± 40 pg/ml vs. 790 ± 40 pg/ml in saline-treated ischemia-reperfusion animals ( P < 0.001). DMOG pretreatment reduced myocardial myeloperoxidase activity, expressed as number of PMN per gram of myocardium, to 1.43 ± 0.59 vs. 4.86 ± 1.1 ( P = 0.012) in saline-treated ischemia-reperfused hearts. Both in vitro and in vivo DMOG-attenuated IL-8 production was associated with robust HO-1 expression. Thus our data show that HIF-1 activation induces substantial HO-1 expression that is associated with attenuated proinflammatory chemokine production by microvascular endothelium in vitro and in vivo.

Novel HIF-1-target gene isthmin1 contributes to hypoxia-induced hyperpermeability of pulmonary microvascular endothelial cells monolayers

2021 ◽  
Author(s):  
Junxia Li ◽  
Yiming Xia ◽  
Zhizhong Huang ◽  
Yan Zhao ◽  
Renping Xiong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Culture System ◽  
Target Gene ◽  
Regulatory Elements ◽  
Alveolar Epithelial Cells ◽  
Microvascular Endothelial Cell ◽  
Pulmonary Microvascular Endothelial Cell ◽  
Microvascular Endothelial

Hypoxia-induced pulmonary microvascular endothelial cell (PMVEC) monolayers hyperpermeability is vital for vascular leakage, which participates in vascular diseases, such as acute lung injury (ALI) and high altitude pulmonary edema (HAPE). We previously observed PMVEC permeability was markedly elevated in hypoxia when cocultured with primary type II alveolar epithelial cells (AECII) in which isthmin1(ISM1) was highly upregulated. However, whether the upregulation of ISM1 plays a role in hypoxia-induced PMVEC hyperpermeability is unclear. In this study, we assessed the role of AECII-derived ISM1 in hypoxia-induced PMVEC hyperpermeability with an AECII/PMVEC co-culture system and uncovered the underlying mechanism whereby hypoxia stimulates ISM1 gene expression. We found that ISM1 gene expression was upregulated in cultured AECII cells exposed to hypoxia (3% O2), and that AECII-derived ISM1 participated in hypoxia-induced hyperpermeability of PMVEC monolayers since siRNA-mediated knockdown of ISM1 in AECII markedly attenuated the increasement of PMVEC permeability in co-culture system under hypoxia. Additionally, we confirmed that ISM1 was regulated by hypoxia-inducible factor-1α (HIF1α) according to the evidence that silencing of HIF1α inhibited the hypoxia-mediated upregulation of ISM1. Mechanismly, overexpression of HIF1α transcriptionally activated ISM1 gene expression by directly binding to the conserved regulatory elements upstream of the ism1 locus. We identified a novel HIF-1-target gene ISM1, which involves in hyperpermeability of pulmonary microvascular endothelial cell monolayers under hypoxia. Our in vitro cell experiments implied that the upregulated ISM1 derived from alveolar epithelium might be a vital modulator in hypoxia-induced endothelial hyperpermeability and thereby implicates with hypoxic pulmonary-related diseases.

Proinflammatory cytokines increase permeability of rat microvascular endothelial cell: Pericyte cocultures in vitro

2004 ◽  
Vol 121 (2) ◽  
pp. 337-338
Author(s):  
S. Kerkar ◽  
M. Williams ◽  
J. Blocksom ◽  
C.P. Steffes ◽  
R.F. Wilson ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Proinflammatory Cytokines ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelial
Sign in / Sign up

Export Citation Format

Share Document