Heterogeneity in lipopolysaccharide responsiveness of endothelial cells identified by gene expression profiling: role of transcription factors

Beck, Grietje; Rafat, Neysan; Brinkkoetter, Paul-Thomas; Hanusch, C; Schulte, Jutta; Haak, Markus; Ackern, K. van; Woude, Fokko J. van der; Yard, Benito A.

doi:10.1111/j.1365-2249.2006.03005.x

Cited by 26 publications

(25 citation statements)

References 47 publications

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“…The present study shows that E-5ЈNu activity is increased after the treatment of LPS, a known inflammation inducer (1,19). This finding is similar to the observation that E-5ЈNu is induced by hypoxia to increase extracellular adenosine, which enhances endothelial barrier function through the activation of adenosine A 2B receptors (7).…”

Section: Discussionsupporting

confidence: 78%

See 1 more Smart Citation

Stimulation of ecto-5′-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide

Man²,

Vanhoutte³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Li RW, Man RY, Vanhoutte PM, Leung GP. Stimulation of ecto-5Ј-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide. Am J Physiol Heart Circ Physiol 295: H1177-H1181, 2008. First published July 18, 2008 doi:10.1152/ajpheart.91513.2007.-The involvement of ecto-5Ј-nucleotidase (E-5ЈNu) in the elevation of extracellular adenosine during inflammation is unclear. In the present study, the effect of lipopolysaccharide (LPS), an inflammation inducer, was investigated on E-5ЈNu in human umbilical vein endothelial cells (HUVECs). E-5ЈNu activity was enhanced after a 24 h exposure to LPS. This effect was dose dependent, with an EC 50 of 1.66 ng/ml. At 10 M, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 abolished the LPS-induced E-5ЈNu activity. However, at 10 M, the NF-B inhibitor ammonium pyrrolidine dithiocarbamate had no effect. LPS upregulated the protein expression but not the messenger RNA expression of E-5ЈNu. The inhibition of E-5ЈNu by 100 M ␣,␤-methylene adenosine-5Ј-diphosphate increased the LPS-induced inflammation, suggesting that E-5ЈNu plays a significant role in reducing inflammation, probably through the generation of adenosine. In conclusion, the experiments indicate that LPS upregulates E-5ЈNu activity in HUVECs through a PI3K-dependent increase in the abundance of E-5ЈNu on cell membranes. Since adenosine is an anti-inflammatory molecule, E-5ЈNu upregulation may be crucial in protecting endothelial cells against inflammatory damage.adenosine; cytokines; inflammation ECTO-5Ј-NUCLEOTIDASE (E-5ЈNu), also known as CD73, is a 70-kDa membrane-bound glycoprotein that is abundant in the endothelium (18). E-5ЈNu extracellularly catalyzes the conversion of purine and pyrimidine ribo-and deoxyribonucleoside monophosphates to their corresponding ribo-and deoxynucleosides. For example, adenosine 5Ј-monophosphate (AMP) is one of the substrates of E-5ЈNu, and adenosine is the corresponding end product (9, 21).Adenosine exerts its effects by interacting with four receptors known as A 1 , A 2A , A 2B , and A 3 receptors (25,27). In addition to its well-known vasodilator and cardioprotective effects (20,23,25), adenosine can also serve as an immunosuppressive agent to minimize tissue damage during inflammation (13,22,25). The stimulation of A 2A receptors downregulates neutrophil functions (25), reduces the recruitment of neutrophil and macrophages to the endothelium (15), and inhibits the production of tumor necrosis factor (TNF)-␣ in peripheral mononuclear white blood cells (4).Endogenous adenosine is increased during inflammation. Since part of the adenosine is derived from the catalytic action of E-5ЈNu, it is plausible that E-5ЈNu activity is subject to change by inflammation and may play an important role in the regulation of the extracellular adenosine level during inflammation. TNF-␣, which is a proinflammatory cytokine, decreases the expression and activity of E-5ЈNu (9), suggesting that less adenosine may be produced to relieve inflammation if E-5ЈNu is downregulated. By ...

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Section: Discussionsupporting

confidence: 78%

“…Therefore, the regulation of E-5ЈNu in inflammation remains controversial, and the enzyme may be regulated differentially by various inflammatory mediators. Therefore, the present study investigated the effects of lipopolysaccharide (LPS), which is widely used as an inducer of inflammation (1,19) on E-5ЈNu in human umbilical vein endothelial cells (HUVECs).…”

mentioning

confidence: 99%

Stimulation of ecto-5′-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide

Man²,

Vanhoutte³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Nuclear extracts were prepared as described previously [15], and protein concentrations were determined by Bradford assay. NF-B (5=-AGTTGAGGGGACTTTC-CCAGGC-3=) or AP-1 (5=-CGCTTGATGACTCAGCCGGAA-3=) doublestranded consensus oligonucleotide (both Promega, Madison, WI, USA) were end-labeled with ␥-32 P-ATP using T4-polynucleotide kinase, ethanolprecipitated, and finally, dissolved in 20 l distilled water.…”

Section: Nuclear Protein Extraction and Emsamentioning

confidence: 99%

N-Octanoyl dopamine transiently inhibits T cell proliferation via G1 cell-cycle arrest and inhibition of redox-dependent transcription factors

Wedel

Hottenrott

Stamellou

et al. 2014

Journal of Leukocyte Biology

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Recently, we developed a nonhemodynamic dopamine derivative, NOD, which has profound anti-inflammatory effects in vitro. As NOD also protects rats from ischemic AKI, the present study tested whether NOD is able to modulate cellular immunity for potential use as a T cell-suppressive agent. To this end, T cells were stimulated by anti-CD3/CD28 or PMA/ionomycin in the presence or absence of different concentrations of NOD. T cell proliferation, activation markers, intracellular cytokine expression, and activation of transcription factors were assessed. Whereas T cell proliferation was inhibited significantly by NOD at Day 3, proliferation was restored at Day 7 or later depending on the NOD concentration used. Inhibition of proliferation was reflected by a diminished CD25 expression and switch from naive to memory T cells. Early TCR activation events were unaffected, yet NF-κB and AP-1 were strongly inhibited by NOD. The inhibitory effect of NOD seemed to be dependent on its redox activity, as NOT, a redox-inactive NOD derivate, did not influence proliferation. NOD displayed synergistic effects with CNIs on T cell proliferation. Our data demonstrate that NOD displays T cell-suppressive activity. In keeping with its anti-inflammatory action and its beneficial effect on ischemia-induced AKI, NOD may be an interesting drug candidate to prevent CNI-related side-effects.

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“…As HUVEC and neutrophils also release IL-8 following LPS stimulation [22,23], we examined whether this response could be affected by apyrase. In contrast to our findings in monocytes, apyrase failed to inhibit IL-8 release from LPS-stimulated HUVEC and neutrophils (Fig.…”

Section: Lps-stimulated Human Endothelial Cells and Neutrophils Releamentioning

confidence: 99%

Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo

Kukulski

Yebdri

Lefebvre

et al. 2007

Journal of Leukocyte Biology

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Extracellular nucleotides are emerging as important inflammatory mediators. Here, we demonstrate that these molecules mediate LPS-induced neutrophil migration in vitro and in vivo. Apyrase, a nucleotide scavenger, reduced the ability of LPS-stimulated monocytes to recruit neutrophils, as assayed using a modified Boyden chamber. This effect resulted from the inhibition of IL-8 release from monocytes. Furthermore, LPS-induced IL-8 release by monocytes was attenuated significantly by P2Y 6 receptor antagonists, RB-2 and MRS2578. Reciprocally, UDP, the selective P2Y 6 agonist, induced IL-8 release by monocytes. As for LPS, the media of UDPstimulated monocytes were chemotactic for neutrophils; IL-8 accounted for ~50% of neutrophil migration induced by the media of LPS-or UDP-treated monocytes in transendothelial migration assays. It is important that in the murine air-pouch model, extracellular nucleotides were instrumental in LPS-induced neutrophil migration. Altogether, these data imply that LPS induces the release of nucleotides from monocytes and that by autocrine stimulation, the latter molecules regulate neutrophil migration caused by Gram-negative bacteria, suggesting a proinflammatory role of extracellular nucleotides in innate immunity.

show abstract

Heterogeneity in lipopolysaccharide responsiveness of endothelial cells identified by gene expression profiling: role of transcription factors

Cited by 26 publications

References 47 publications

Stimulation of ecto-5′-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide

Stimulation of ecto-5′-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide

N-Octanoyl dopamine transiently inhibits T cell proliferation via G1 cell-cycle arrest and inhibition of redox-dependent transcription factors

Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo

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