Retinoic acid reduces induction of monocyte tissue factor and tissue factor/factor VIIa-dependent arterial thrombus formation

Barstad, R. M.; Hamers, M. J. A. G.; Stephens, Ross W.; Sakariassen, Kjell S.

doi:10.1182/blood.v86.1.212.bloodjournal861212

Cited by 46 publications

(12 citation statements)

References 33 publications

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“…TF expression is also downregulated by all‐ trans ‐retinoic acid, which is a ligand for a nuclear receptor family known as the retinoic acid receptors (RARs) [45–47]. In RAR activation, unlike LXR, the inhibitory effect appears to be independent of the NFκB or AP‐1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Liver X receptor agonists inhibit tissue factor expression in macrophages

Terasaka¹,

Hiroshima²,

Ariga³

et al. 2005

The FEBS Journal

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Exposure of blood to tissue factor (TF) rapidly initiates the coagulation serine protease cascades. TF is expressed by macrophages and other types of cell within atherosclerotic lesions and plays an important role in thrombus formation after plaque rupture. Macrophage TF expression is induced by pro‐inflammatory stimuli including lipopolysaccharide (LPS), interleukin‐1β and tumor necrosis factor‐α. Here we demonstrate that activation of liver X receptors (LXRs) LXRα and LXRβ suppresses TF expression. Treatment of mouse peritoneal macrophages with synthetic LXR agonist T0901317 or GW3965 reduced TF expression induced by pro‐inflammatory stimuli. LXR agonists also suppressed TF expression and its activity in human monocytes. Human and mouse TF promoters contain binding sites for the transcription factors AP‐1, NFκB, Egr‐1 and Sp1, but no LXR‐binding sites could be found. Cotransfection assays with LXR and TF promoter constructs in RAW 264.7 cells revealed that LXR agonists suppressed LPS‐induced TF promoter activity. Analysis of TF promoter also showed that inhibition of TF promoter activity by LXR was at least in part through inhibition of the NFκB signaling pathway. In addition, in vivo, LXR agonists reduced TF expression within aortic lesions in an atherosclerosis mouse model as well as in kidney and lung in mice stimulated with LPS. These findings indicate that activation of LXR results in reduction of TF expression, which may influence atherothrombosis in patients with vascular disease.

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Section: Discussionmentioning

confidence: 99%

Liver X receptor agonists inhibit tissue factor expression in macrophages

Terasaka¹,

Hiroshima²,

Ariga³

et al. 2005

The FEBS Journal

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“…Derivates of retinoic acid have been shown earlier to have anticoagulant effects on monocytic cells (24,25). It has been reported, that ATRA up-regulates thrombomodulin and down-regulates T F expression in primary leukaemic cells (26), and in the established leukaemic cell lines of the monocytic lineage (25).…”

Section: Discussionmentioning

confidence: 99%

Induction of differentiation in U‐937 and NB4 cells is associated with inhibition of tissue factor production

Tenno

Öberg

Nilsson

et al. 1999

European J of Haematology

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Tissue factor (TF) production is under strict control in mature monocytic cells. However, constitutive expression of TF can be found in myelomonocytic cells and in haematopoietic cells arrested at an early stage of differentiation. In this paper we show that TF expression is down‐regulated during the monocyte/granulocyte differentiation process, using the human monoblastic U‐937 and the acute promyelocytic leukaemia NB4 cell lines as models. Expression of TF mRNA, protein and procoagulant activity (PCA) was constitutively high in untreated cells. Exposure of U‐937 cells to 1 α,25‐dihydroxycholecalciferol (VitD3) and all‐trans retinoic acid (ATRA) resulted in down‐regulation of TF expression and PCA. In NB4 cells induction by ATRA, but not VitD3, resulted in the down‐regulation of TF expression and PCA. Consistent with this, induction of terminal differentiation, as confirmed by the expression of differentiation associated antigens and cell cycle arrest, was inversely correlated to TF expression in U‐937 and NB4 cells. Moreover, terminally differentiated U‐937 cells retained the capacity to respond to inflammatory mediators, i.e. lipopolysaccharide and interferon‐γ, by a rapid increase in TF expression. In conclusion, we show that not only ATRA but also VitD3 is a potent suppressor of monocytic TF expression and thus might have potential clinical use for the treatment of coagulopathies.

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“…Alternatively, TF-mediated tumor angiogenesis, rather than coagulation activation, may promote growth of this tumor type. Retinoids inhibit cellular TF expression in monocytes (31), alveolar macrophages (32), and acute myelogenous leukemia cells (33). Retinoids prevent transformation of premalignant head and neck lesions into malignancy (34), the appearance of second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck (35), and the growth of the head and neck squamous cell cancer cell lines in culture (36).…”

Section: Discussionmentioning

confidence: 99%

Expression of Tissue Factor and Tissue Factor Pathway Inhibitor in situ in Laryngeal Carcinoma

Wojtukiewicz

Zacharski²,

Rucińska³

et al. 1999

Thromb Haemost

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SummaryThe blood coagulation mechanism may support tumor progression by several mechanisms including promotion of cell proliferation and angiogenesis. Immunohistochemical procedures were applied to AMeX-fixed sections of twelve cases of squamous cell carcinoma of the larynx obtained at surgical resection to determine the presence and distribution of tissue factor (TF), tissue factor pathway inhibitor (TFPI), other coagulation factors, fibrinogen, and fibrin in situ. TF antigen was present in normal squamous epithelial cells and tumor cells, predominantly in immature tumor cells in the vicinity of the host-tumor interface. Tumor cells stained also for factors VII and X. Staining for TFPI antigen was demonstrated in the connective tissue stroma adjacent to the tumor, in microvascular endothelial cells, and in normal squamous epithelial cells. Fibrinogen and factor XIIIa were distributed throughout the tumor connective tissue stroma. Fibrin (thrombin-cleaved fibrinogen) was detected at the host-tumor interface and along the margins of tumor nodules. Tumor cells in carcinoma of the larynx express a functional, TF-initiated pathway of blood coagulation. Interpretation of these findings together with the results of clinical trials of inhibitors of TF-induced coagulation activation versus effects of inhibitors of TF expression suggest novel approaches to the experimental therapy of laryngeal carcinoma.

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Retinoic acid reduces induction of monocyte tissue factor and tissue factor/factor VIIa-dependent arterial thrombus formation

Cited by 46 publications

References 33 publications

Liver X receptor agonists inhibit tissue factor expression in macrophages

Liver X receptor agonists inhibit tissue factor expression in macrophages

Induction of differentiation in U‐937 and NB4 cells is associated with inhibition of tissue factor production

Expression of Tissue Factor and Tissue Factor Pathway Inhibitor in situ in Laryngeal Carcinoma

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