Naftidrofuryl-driven regulation of endothelial ICAM-1 involves nitric oxide

Marconi, Anthony; Darquenne, Sophie; Boulmerka, A; Mosnier, M.; d’Alessio, Patrizia

doi:10.1016/s0891-5849(02)01368-0

Cited by 21 publications

(9 citation statements)

References 40 publications

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“…This indicates that serotonin might influence leukocyte recruitment by interacting with endothelial cells. Marconi et al found in 2003 that blocking of 5-HT2 receptors with naftidrofuryl inhibited the TNF-α-triggered expression of ICAM-1 expression and stress fiber formation in human umbilical vein endothelial cells ( via NO release) (107). Our group found in 2014 that E-selectin expression on endothelium was upregulated upon higher serotonin levels in plasma (33).…”

Section: Serotonin Effects On Vascular Smooth Muscle Cells and Endothmentioning

confidence: 99%

The Effects of Serotonin in Immune Cells

Herr

Bode

Duerschmied

2017

Front. Cardiovasc. Med.

342

298

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Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express at least one serotonin component. In recent years, a number of immunoregulatory functions have been ascribed to serotonin. In monocytes/macrophages, for example, serotonin modulates cytokine secretion. Serotonin can also suppress the release of tumor necrosis factor-α and interleukin-1β by activating serotonin receptors. Furthermore, neutrophil recruitment and T-cell activation can both be mediated by serotonin. These are only a few of the known immunomodulatory roles of serotonin that we will review here.

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Section: Serotonin Effects On Vascular Smooth Muscle Cells and Endothmentioning

confidence: 99%

The Effects of Serotonin in Immune Cells

Herr

Bode

Duerschmied

2017

Front. Cardiovasc. Med.

342

298

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“…Human umbilical vein endothelial cell (HUVEC) isolation and culture HUVEC were collected following normal deliveries from nonhypertensive, nondiabetic, nonsmoking women, as we described previously [24]. Cells were passaged in 25 cm 2 culture flasks in 5% CO 2 humidified air at 37°C in EGM2 supplemented with FBS (final concentration 5%, v/v), hFGF-B (0.4%), VEGF (0.1%), IGF (0.4%), R 3 -IGF-1 (0.1%), hEGF (0.1%), penicillin, and streptomycin.…”

Section: Reagentsmentioning

confidence: 99%

Tripterine inhibits the expression of adhesion molecules in activated endothelial cells

Zhang

Marconi

et al. 2006

Journal of Leukocyte Biology

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Cell adhesion molecules (CAM) expressed by vascular endothelium in response to cytokine stimulation play a key role in leukocyte adhesion to endothelium during the inflammatory response. Tripterine, a chemical compound of the Chinese plant Tripterygium wilfordii Hook f, displays anti-inflammatory properties in several animal models. However, mechanisms of its action are poorly understood. In the present study, we show that in inflammatory conditions, mimicked by tumor necrosis factor alpha (TNF-alpha) stimulation, pretreatment for 6 h with tripterine at nontoxic concentrations of 20-200 nM inhibits the expression of E-selectin, vascular cell adhesion molecule (CAM)-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. Tripterine (200 nM) almost completely inhibits expression of VCAM-1 [50% inhibitory concentration (IC50) = 52 nM] and ICAM-1 (IC50 = 51 nM) and 73% of E-selectin (IC50 = 94 nM). This inhibition effect is prominent, compared with that of dexamethasone, ibuprofen, methotrexate, or probucol, which revealed a much weaker inhibition at doses as high as 1 mM. Effects on endothelial CAM of other proinflammatory cytokines, such as interleukin-1beta and interferon-gamma, were also inhibited significantly by tripterine. Moreover, significant inhibition was equally observable in postincubation experiments. In addition, tripterine inhibited adhesion of human monocytes and T lymphocytes to TNF-alpha-stimulated HUVEC. Finally, tripterine inhibited TNF-alpha-driven CAM mRNA transcription and nuclear factor-kappaB nuclear (NF-kappaB) translocation. Hence, we describe a new mechanism of tripterine's anti-inflammatory action obtained at nanomolar concentrations, owing to the negative regulation of cytokine-induced adhesion molecule expression and adhesiveness in human endothelium.

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“…However, the role of 5-HT 2A receptors in inflammatory processes is unclear, with only a very few published and inconsistent reports. Some studies report that blockade of 5-HT 2A receptor function with the selective antagonist sarpogrelate can decrease expression of proinflammatory markers (Marconi et al, 2003;Akiyoshi et al, 2006), whereas others indicate that sarpogrelate can increase expression of proinflammatory markers (Ito et al, 2000). Cloëz-Tayarani et al (2003) have alleged that the 5-HT 2 receptor-specific agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) represses interleukin (IL)-1␤ expression and production of tumor necrosis factor-␣ (TNF-␣) through 5-HT 2A receptor activation.…”

mentioning

confidence: 99%

Serotonin 5-Hydroxytryptamine_2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation with Extraordinary Potency

Yu¹,

Becnel²,

Zerfaoui³

et al. 2008

J Pharmacol Exp Ther

167

129

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The G protein-coupled serotonin 5-hydroxytryptamine (5-HT) 2A receptor is primarily recognized for its role in brain neurotransmission, where it mediates a wide variety of functions, including certain aspects of cognition. However, there is significant expression of this receptor in peripheral tissues, where its importance is largely unknown. We have now discovered that activation of 5-HT 2A receptors in primary aortic smooth muscle cells provides a previously unknown and extremely potent inhibition of tumor necrosis factor (TNF)-␣-mediated inflammation. 5-HT 2A receptor stimulation with the agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(R)-DOI] rapidly inhibits a variety of TNF-␣-mediated proinflammatory markers, including intracellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), and interleukin (IL)-6 gene expression, nitric-oxide synthase activity, and nuclear translocation of nuclear factor B, with IC 50 values of only 10 to 20 pM.It is significant that proinflammatory markers can also be inhibited by (R)-DOI hours after treatment with TNF-␣. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. TNF-␣-mediated inflammatory pathways have been strongly implicated in a number of diseases, including atherosclerosis, rheumatoid arthritis, psoriasis, type II diabetes, depression, schizophrenia, and Alzheimer's disease. Our results indicate that activation of 5-HT 2A receptors represents a novel, and extraordinarily potent, potential therapeutic avenue for the treatment of disorders involving TNF-␣-mediated inflammation. Note that because (R)-DOI can significantly inhibit the effects of TNF-␣ many hours after the administration of TNF-␣, potential therapies could be aimed not only at preventing inflammation but also treating inflammatory injury that has already occurred or is ongoing.Serotonin, 5-hydroxytryptamine (5-HT), is a small monoamine molecule primarily known for its role as a neurotransmitter. Within the brain, it modulates a variety of behaviors including cognition, mood, aggression, mating, feeding, and sleep . These behaviors are mediated through interactions at seven different receptor families (5-HT 1-7 ) comprised of 14 distinct subtypes . Each of these are G protein-coupled receptors, with the exception of the 5-HT 3 receptor, which is a ligandgated ion channel. Of all the serotonin receptors, the 5-HT 2A receptor, which is known to primarily couple to the G␣q effector pathway (Roth et al., 1986), has been the one most closely linked to complex behaviors. There is a high level of expression within the frontal cortex, with significant localization to the apical dendrites of cortical pyramidal cells (Willins et al., 1997), and further expression at lower levels PKC, protein kinase C; Gö 6976, 5,6,7,pyrrolo [3,4-c]carbazole-12-propanenitrile; PMA, phorbol 12-myristate 13-acetate; F-22, fragment 6 -22; LA-SS-Az, (2ЈS,4ЈS)-(ϩ)-9,10-didehydro-6-methylergoli...

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Naftidrofuryl-driven regulation of endothelial ICAM-1 involves nitric oxide

Cited by 21 publications

References 40 publications

The Effects of Serotonin in Immune Cells

The Effects of Serotonin in Immune Cells

Tripterine inhibits the expression of adhesion molecules in activated endothelial cells

Serotonin 5-Hydroxytryptamine_2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation with Extraordinary Potency

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Naftidrofuryl-driven regulation of endothelial ICAM-1 involves nitric oxide

Cited by 21 publications

References 40 publications

The Effects of Serotonin in Immune Cells

The Effects of Serotonin in Immune Cells

Tripterine inhibits the expression of adhesion molecules in activated endothelial cells

Serotonin 5-Hydroxytryptamine2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation with Extraordinary Potency

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Product

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About

Serotonin 5-Hydroxytryptamine_2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation with Extraordinary Potency