Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin‐activated human monocytes

Ollivier, Véronique; Ternisien, Catherine; Vu, Thi An; Hakim, Jacques; Prost, Dominique de

doi:10.1016/0014-5793(93)81576-l

Cited by 23 publications

(15 citation statements)

References 16 publications

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“…Pentoxifylline, a methylxanthine with hemorheologic effects, has been shown to inhibit monocyte TF expression induced by LPS. 26,27 Several angiotensinconverting enzyme inhibitors (captopril, imidapril, and fosinopril) significantly inhibit LPS-induced monocyte TF activity, antigen expression, and gene transcription. 28,29 Finally, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (simvastatin, fluvastatin) reduce TF activity, antigen expression, and gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep

Zhou

Wolberg

Roubey

2004

Blood

142

107

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Increasing evidence suggests that autoantibodies directly contribute to hypercoagulability in the antiphospholipid syndrome (APS). One proposed mechanism is the antibody-induced expression of tissue factor (TF) by blood monocytes. Dilazep, an antiplatelet agent, is an adenosine uptake inhibitor known to block induction of monocyte TF expression by bacterial lipopolysaccharide. In the current study we characterized the effects of immunoglobulin G (IgG) from patients with APS on monocyte TF activity and investigated whether dilazep is capable of blocking this effect. IgG from 13 of 16 patients with APS significantly increased monocyte TF activity, whereas normal IgG had no effect. Time-course experiments demonstrated that APS IgG-induced monocyte TF mRNA levels were maximal at 2 hours and TF activity on the cell surface was maximal at 6 hours. Dilazep inhibited antibody-induced monocyte TF activity in a dose-dependent fashion but had no effect on TF mRNA expression. The effect of dilazep was blocked by theophylline, a nonspecific adenosine receptor antagonist. In conclusion, IgG from certain patients with APS induce monocyte TF activity. Dilazep inhibits the increased expression of monocyte TF activity at a posttranscriptional level, probably by way of its effect as an adenosine uptake inhibitor. Pharmacologic agents that block monocyte TF activity may be a novel therapeutic approach in APS. IntroductionIt is widely hypothesized that autoantibodies directly contribute to hypercoagulability in patients with the antiphospholipid syndrome (APS), and numerous pathophysiologic mechanisms have been proposed. Once such mechanism is the antibody-induced expression of tissue factor (TF; CD142) on monocytes or vascular endothelial cells, or both. 1 TF is an integral membrane protein constitutively expressed in many cell types outside of the vasculature, but it is not normally expressed on cells that are in contact with flowing blood. It is a specific and high-affinity receptor for factor VII/VIIa and functions as a cofactor for factor VIIa enzymatic activity. Exposure of active TF to blood triggers physiologic blood coagulation and thrombosis in a wide variety of thrombotic diseases. 2 Blood monocytes do not constitutively express functional TF; however, they are capable of TF synthesis and expression when stimulated with lipopolysaccharide (LPS) or certain inflammatory cytokines. 3 Expression of TF on monocytes has been implicated as a mechanism of thrombosis in several conditions, including sepsis, 4 atherosclerosis, 5 the use of oral contraceptives, 6 cancer, 7 and hyperhomocysteinemia. 8 There is growing evidence that certain types of antiphospholipid antibodies, particularly those directed against ␤ 2 -glycoprotein I (␤2GPI), stimulate monocyte tissue factor expression in patients with APS. 9,10 Current treatment for the prevention of recurrent thrombosis in patients with APS is a high level of anticoagulation with warfarin. The identification of specific mechanisms of hypercoagulability in APS may allow for more spec...

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Section: Discussionmentioning

confidence: 99%

Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep

Zhou

Wolberg

Roubey

2004

Blood

142

107

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“…In contrast, its downregulation has been reported including by HMG-CoA reductase inhibitors [33, 34], cyclooxygenase (COX) inhibitors [35–37], paclitaxel [38], lysophosphatidylcholine [39], insulin [40], nicotinamide [41], nitric oxide (NO)/or soluble guanylate cyclase activator [42], hydroxyurea [43], ethyl pyruvate [44], dimethyl sulfoxide (DMSO) [45], angiotensin converting enzyme (ACE) inhibitors [46], adiponectin [47], retinoic acid [48], all-trans retinoic acid [49], vitamin D3 [50], PGJ2 [51], PPAR α agonists (fenofibric acid, WY14643, and GW2331) [52]/activators (WY14643 and eicosatetraenoic acid) [53], liver X receptor agonists [54], pentroxifylline [55], phenolics/resveratrol derivatives [56], indobufen [57], amiodarone [58], metformin [59], elevated intracellular cAMP [4], and PI3K/Akt/PKB signaling [60]. On the molecular biology front, miR-19 [61], short hairpin RNA [62], hairpin ribozyme [63], or antisense ODN [64–66] readily downregulates TF mRNA translation and expression.…”

Section: Regulation Of Tissue Factor Expressionmentioning

confidence: 99%

Tissue Factor, Blood Coagulation, and Beyond: An Overview

Chu

2011

International Journal of Inflammation

178

184

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Emerging evidence shows a broad spectrum of biological functions of tissue factor (TF). TF classical role in initiating the extrinsic blood coagulation and its direct thrombotic action in close relation to cardiovascular risks have long been established. TF overexpression/hypercoagulability often observed in many clinical conditions certainly expands its role in proinflammation, diabetes, obesity, cardiovascular diseases, angiogenesis, tumor metastasis, wound repairs, embryonic development, cell adhesion/migration, innate immunity, infection, pregnancy loss, and many others. This paper broadly covers seminal observations to discuss TF pathogenic roles in relation to diverse disease development or manifestation. Biochemically, extracellular TF signaling interfaced through protease-activated receptors (PARs) elicits cellular activation and inflammatory responses. TF diverse biological roles are associated with either coagulation-dependent or noncoagulation-mediated actions. Apparently, TF hypercoagulability refuels a coagulation-inflammation-thrombosis circuit in “autocrine” or “paracrine” fashions, which triggers a wide spectrum of pathophysiology. Accordingly, TF suppression, anticoagulation, PAR blockade, or general anti-inflammation offers an array of therapeutical benefits for easing diverse pathological conditions.

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“…The aim of this work was to assess the effect of interleukin-10 (IL-lo) and that of pcntoxifylline @'TX), a methylxanthine derivative [1- (5-oxo-hexyl)-3,7_dimethylxanthine] (Torental, Hoechst), on CRP-induced TF activity, TF antigen and mRNA expression. These two compounds have been shown to downregulate LPS-induced TF synthesis [5,6] and have great potential therapeutic value.…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐10 and pentoxifylline inhibit C‐reactive protein‐induced tissue factor gene expression in peripheral human blood monocytes

et al. 1994

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Fibrin deposition is au integral feature of the inflammatory response. In response to C-reactive protein (CRP), an acute-phase reactant, blood monocytes synthesize and express tissue factor (TF), the main initiator of blood coagulation. We report the inhibitory effect of interleukin 10 (IL-IO) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA iu response to CRP. These agents may be of use in diseases where a TF-induced prothrombotic state is detrimental.

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Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin‐activated human monocytes

Cited by 23 publications

References 16 publications

Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep

Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep

Tissue Factor, Blood Coagulation, and Beyond: An Overview

Interleukin‐10 and pentoxifylline inhibit C‐reactive protein‐induced tissue factor gene expression in peripheral human blood monocytes

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