Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability

Reddy, Krishna; Bhattacharjee, Gourab; Schabbauer, Gernot; Hollis, Angela; Kempf, Kevin; Tencati, Michael; O’Connell, Maria A.; Guha, Mausumee; Mackman, Nigel

doi:10.1189/jlb.0204068

Cited by 34 publications

(29 citation statements)

References 45 publications

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“…Because thrombin stimulation induces multiple side effects and is thus not advisable for in vivo treatment, mice were treated with dexamethasone, known to induce Sgk-1 and TF. 7,25 TF protein levels were enhanced in lung tissue derived from dexamethasone-treated sgk-1 ϩ/ϩ but not from sgk1 Ϫ/Ϫ mice ( Figure 4E). Similarly, TF activity in lung extracts derived from sgk1 ϩ/ϩ , but not from sgk1 Ϫ/Ϫ mice, was significantly enhanced by dexamethasone ( Figure 4F).…”

Section: Sgk-1 Is Involved In Tissue Factor Expression and Activity Bmentioning

confidence: 89%

“…Ϫ/Ϫ fibroblasts stimulated with thrombin or in lung tissue from sgk1 Ϫ/Ϫ mice treated with dexamethasone, known to stimulate TF 25 and Sgk-1. 7 The importance of Sgk-1 for thrombin-induced TF expression is further supported by our previous findings that TF mRNA and protein expression peak at 4 and 8 hours of stimulation with thrombin in PASMC, respectively, 17 thus clearly following the upregulation of Sgk-1.…”

Section: Over Tf Expression Was Not Detectable In Sgk1mentioning

confidence: 99%

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The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling

BelAiba

Bonello

Artunc

et al. 2006

Circulation Research

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Abstract-The stress-responsive serum-and glucocorticoid-inducible kinase Sgk-1 is involved in osmoregulation and cell survival and may contribute to fibrosis and hypertension. However, the function of Sgk-1 in vascular remodeling and thrombosis, 2 major determinants of pulmonary hypertension (PH), has not been elucidated. We investigated the role of Sgk-1 in thrombin signaling and tissue factor (TF) expression and activity in pulmonary artery smooth muscle cells (PASMC). Thrombin increased Sgk-1 activity and mRNA and protein expression. H 2 O 2 similarly induced Sgk-1 expression. Antioxidants, dominant-negative Rac, and depletion of the NADPH oxidase subunit p22phox diminished thrombin-induced Sgk-1 expression. Inhibition of p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and phosphoinositide-dependent kinase-1 prevented thrombin-induced Sgk-1 expression. Thrombin or Sgk-1 overexpression enhanced TF expression and procoagulant activity, whereas TF upregulation by thrombin was diminished by kinase-deficient Sgk-1 and was not detectable in fibroblasts from mice deficient in sgk-1 (sgk1 Ϫ/Ϫ ). Similarly, dexamethasone treatment failed to induce TF expression and activity in lung tissue from sgk1 Ϫ/Ϫ mice. Transcriptional induction of TF by Sgk-1 was mediated through nuclear factor B. Finally, Sgk-1 and TF proteins were detected in the media of remodeled pulmonary vessels associated with PH. These data show that thrombin potently induces Sgk-1 involving NADPH oxidases, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and phosphoinositide-dependent kinase-1, and that activation of nuclear factor B by Sgk-1 mediates TF expression and activity by thrombin. Because enhanced procoagulant activity can promote pulmonary vascular remodeling, and Sgk-1 and TF were present in the media of remodeled pulmonary vessels, this pathway may play a critical role in vascular remodeling in PH. Key Words: sgk-1 Ⅲ thrombin Ⅲ tissue factor Ⅲ NADPH oxidase Ⅲ coagulant activity Ⅲ pulmonary vascular remodeling Ⅲ pulmonary artery smooth muscle cells Ⅲ nuclear factor B P ulmonary hypertension (PH) is a complex progressive disorder characterized by remodeling of the lung vasculature with hypertrophy of the media. 1 Moreover, a prothrombotic state is frequently associated with PH, which may be propagated by enhanced thrombogenicity of the injured pulmonary vascular wall, increased thrombin activity, and an imbalance between prothrombotic and antithrombotic factors. The observation that antithrombotic treatment can improve the survival rate in patients with PH points toward the importance of thrombosis in the pathogenesis of this disorder.

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Section: Sgk-1 Is Involved In Tissue Factor Expression and Activity Bmentioning

confidence: 89%

Section: Over Tf Expression Was Not Detectable In Sgk1mentioning

confidence: 99%

The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling

BelAiba

Bonello

Artunc

et al. 2006

Circulation Research

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“…Some stimulants such as arachidonic acid, but not others (e.g., LPS (52)), increase monocyte TF via production of cyclooxygenase metabolites (53), but indomethacin did not influence induction even though SAA increases cyclo-oxygenase metabolites in activated human monocytes (54). Glucocorticoids are clinically useful in treating inflammatory disorders, but, as in other systems, dexamethasone did not reduce TF levels on monocytes stimulated with SAA, and unlike its effect on LPS (33), no enhancement was observed.…”

Section: Discussionmentioning

confidence: 99%

“…Because most of the RA patients were on corticosteroid treatment, dexamethasone was used to determine whether steroids had any effect on SAA induction of TF. Although dexamethasone can enhance LPS induction of TF (33), it had no significant effect on SAAinduced TF in concentrations from 10 Ϫ7 to 10 Ϫ5 M. The cyclooxygenase inhibitor indomethacin also failed to affect TF induction significantly (Fig. 6A).…”

Section: Mechanisms Of Tf Induction By Saamentioning

confidence: 93%

Serum Amyloid A Induces Monocyte Tissue Factor

Cai

Song

Endoh

et al. 2007

The Journal of Immunology

107

121

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C-reactive protein (CRP) and serum amyloid A (SAA) increase in the blood of patients with inflammatory conditions and CRP-induced monocyte tissue factor (TF) may contribute to inflammation-associated thrombosis. This study demonstrates that SAA is a potent and rapid inducer of human monocyte TF. SAA induced TF mRNA in PBMC within 30 min and optimal procoagulant activity within 4 h, whereas CRP (25 μg/ml)-induced activity was minimal at this time. Unlike CRP, SAA did not synergize with LPS. Procoagulant activity was inhibited by anti-TF and was dependent on factors VII and X, and TF Ag levels were elevated on CD14+ monocytes. Responses were optimal with lymphocytes, although these were not obligatory. Inhibitor studies indicate activation of NF-κB through the ERK1/2 and p38 MAPK pathways; the cyclo-oxygenase pathway was not involved. SAA-induced TF was partially inhibited by high-density lipoprotein, but not by low-density lipoprotein or by apolipoprotein A-I. SAA is a ligand for the receptor for advanced glycation end products (RAGE), and TF generation was suppressed by ∼50% by a RAGE competitor, soluble RAGE, and by ∼85% by anti-RAGE IgG. However, another RAGE ligand, high mobility group box-1 protein, capable of inducing monocyte chemotactic protein-1 mRNA in 2 h, did not induce TF within 24 h. Cross-linking studies confirmed SAA binding to soluble RAGE. Elevated SAA is a marker of disease activity in patients with rheumatoid arthritis, and PBMC from patients with rheumatoid arthritis were more sensitive to SAA than normals, suggesting a new link between inflammation and thrombosis.

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“…estrogen, in cigarette smokers and in hyperhomocysteinemia [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] .…”

Section: Inflammationmentioning

confidence: 99%

The role of tissue factor in normal pregnancy and in the development of preeclampsia: A review

Procházková¹,

Slavík²,

Úlehlová³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Tissue factor (TF) is a key element for normal gestation, especially in the first trimester. TF levels are hence raised in pregnancy, producing an adaptive hypercoagulable state. Potentiated hypercoagulability however, is associated with disorders of pregnancy such as pre-eclampsia but the results of TF and its inhibitor, tissue factor pathway inhibitor (TFPI), measurement, in pre eclampsic women are ambiguous and the data conflicting. This review covers the current knowledge status of the role of TF assessment in pregnancy with a focus on its diagnostic utility. Methods. A review of the literature using the following key words: tissue factor, thrombosis, inflammation, pregnancy, preeclampsia.Results. The published literature shows raised and unchanged TF levels in various studies of pre-eclampsia along with equally conflicting data for TFPI. The various study designs and methods used in these studies makes valid comparison difficult. Meta analysis of 34 randomized trials showed that low-dose aspirin in early phases of gravidity (starting from the 16th week or earlier) significantly reduces the incidence of preeclampsia. Conclusions. Overall, the results of the literature search together with knowledge of the structure and biological effects of TF, suggest that measuring the level of plasma TF/TFPI is not ideal for determining the actual levels of TF in the uteroplacental circulation. The current view that endothelial dysfunction is the trigger for preeclampsia, suggests that aspirin may be an effective prophylaxis. Further research will be necessary: measuring the expression of tissue factor on monocytes using flowcytometry and comparing the development of this expression during normal pregnancy and pregnancy complicated by preeclampsia, for example. Another possibility is immunohistochemical determination of the level of TF expression directly in placental tissue.

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Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability

Cited by 34 publications

References 45 publications

The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling

The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling

Serum Amyloid A Induces Monocyte Tissue Factor

The role of tissue factor in normal pregnancy and in the development of preeclampsia: A review

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