Histamine Induces Tissue Factor Expression

Steffel, Jan; Akhmedov, Alexander; Greutert, Helen; Lüscher, Thomas F.; Tanner, Felix C.

doi:10.1161/circulationaha.105.553735

Cited by 130 publications

(89 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data from the experiments investigating the intracellular signaling cascade demonstrate that ERK MAPK mediates histamine-induced Egr-1 expression. The role of MAPK in histamine induction of endothelial gene expression has not been well explored, although a previous report suggested that ERK, p38, and JNK MAPK may all contribute to histamine induction of tissue factor expression (11). Our data clearly show that activation of ERK, but not of JNK or p38, is required for histamineinduced Egr-1 expression.…”

Section: Discussionmentioning

confidence: 46%

“…One of these studies showed that the histamine H1 receptor antagonist reduced intimal hyperplasia (13); the other study reported that histamine synthesis enzyme knock-out mice (HDC Ϫ/Ϫ mice) showed reduced neointimal thickening and a decreased intima-to-media thickness ratio (14). In regard to how histamine influences inflammation and atherosclerosis in endothelial cells, evidence has shown that histamine induces expression of genes such as p-selectin (9), ICAM1, VCAM1 (10), IL6, IL8 (8), cyclooxygenase-2 (27), and tissue factor (11). The products of these genes have been shown to promote inflammation and atherogenesis (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…Histamine induces endothelial cells to produce proinflammatory cytokines such as interleukin 6 (IL6) and interleukin 8 (IL8) (6 -8); adherent molecules such as p-selectin (9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) (10), and tissue factor (11), a prominent initiator of blood coagulation. Histamine also induces tissue factor expression in smooth muscle cells (11), and smooth muscle cell proliferation (12,13). Most importantly, the antagonists of histamine receptor 1 (H1) reduce thickened intimas in mice (13), and recently, HDC knock-out mice showed reduced neointimal thickening (14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cδ-dependent ERK Activation Pathway

Feng

Tan

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Histamine, a potent inflammatory mediator, has multiple effects on the pathogenesis of atherosclerosis. This study investigates the effect of histamine on the expression of early growth response factor 1 (Egr-1), a master transcription factor that regulates the expression of an array of atherogenic genes in atherosclerotic lesions. Histamine markedly and rapidly induces Egr-1 mRNA and protein expression in primary human aortic endothelial cells (HAECs). Histamine-induced Egr-1 expression is dependent on the activation of the H1 receptor. Histamine also rapidly and transiently activates protein kinase C-␦ (PKC␦), extracellular signal-regulated kinase (ERK)1/2, p38 kinase, and c-Jun N-terminal kinase (JNK) prior to Egr-1 induction. Using specific pharmacological inhibitors and small interfering RNA technology, we determined that PKC␦ and ERK, but not p38 and JNK, mediate histamine-induced Egr-1 expression. Our data provide the first evidence that histamine regulates expression of Egr-1 in mammalian cells and demonstrate a novel role of PKC␦ in up-regulation of Egr-1 expression. The present study reveals the following regulatory mechanism: histamine up-regulates Egr-1 expression in primary HAECs via the H1 receptor and the PKC␦-dependent ERK activation pathway. Our data also imply that CREB, a downstream component of the ERK pathway, regulates Egr-1 expression in HAECs. Importantly, these results suggest a central role of Egr-1 in histamine-induced gene expression and in histamine-induced vascular disease.

show abstract

Section: Discussionmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cδ-dependent ERK Activation Pathway

Feng

Tan

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…MAP kinase activation mediates endothelial TF expression by promoting transcription in response to many stimuli (4,22) and earlier studies have shown that MAPK activation is required for PI3K-dependent TF activation. Accordingly, p38, ERK, and JNK were transiently activated by TNF-α.…”

Section: Discussionmentioning

confidence: 99%

“…Protein expression was determined by Western blot analysis as described (22). Equal loading was confirmed by Ponceau S staining.…”

Section: Western Blotmentioning

confidence: 99%

Caffeine induces endothelial tissue factor expression via phosphatidylinositol 3-kinase inhibition

Gebhard¹,

Holy²,

Camici³

et al. 2012

Thromb Haemost

Self Cite

View full text Add to dashboard Cite

SummaryTissue factor (TF) is the key activator of coagulation and is involved in acute coronary syndromes. Caffeine is often reported to increase cardiovascular risk; however, its effect on cardiovascular morbidity and mortality is controversial. Hence, this study was designed to investigate the impact of caffeine on endothelial TF expression in vitro. Caffeine concentration-dependently enhanced TF protein expression and surface activity in human endothelial cells stimulated by tumour necrosis factor (TNF)-α or thrombin. Caffeine inhibited phosphatidylinositol 3-kinase (PI3K) activity and this effect was comparable to that of the known PI3K inhibitor LY294002. Consistently, treatment of endothelial cells with LY294002 enhanced TNF-α induced TF expression to a similar extent as caffeine, and adenoviral expression of the active PI3K mutant (p110) reversed the effect of both caffeine and LY294002 on TF expression. Caffeine and LY294002 increased DNA binding capacity of the transcription factor nuclear factor κB, whereas the activation pattern of mitogen-activated protein kinases (MAPK) remained unaltered. Luciferase reporter assay revealed a caffeine dependent activation of the TF promoter, and RT-PCR revealed a dose dependent increase in TF mRNA levels when stimulated with caffeine in the presence of TNF-α. In conclusion, caffeine enhances TNF-α-induced endothelial TF protein expression as well as surface activity by inhibition of PI3K signalling. Since the caffeine concentrations applied in the present study are within the plasma range measured in humans, our findings indicate that caffeine enhances the prothrombotic potential of endothelial cells and underscore the importance of PI3K in mediating these effects.

show abstract

Umbilical Cord Derived Mast Cells as Models for the Study of Inflammatory Diseases

Kourelis¹,

Kempuraj²,

Manola³

et al. 2009

Perinatal Stem Cells

View full text Add to dashboard Cite

Histamine Induces Tissue Factor Expression

Cited by 130 publications

References 52 publications

Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cδ-dependent ERK Activation Pathway

Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cδ-dependent ERK Activation Pathway

Caffeine induces endothelial tissue factor expression via phosphatidylinositol 3-kinase inhibition

Umbilical Cord Derived Mast Cells as Models for the Study of Inflammatory Diseases

Contact Info

Product

Resources

About