von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells

Teysseire, N; Arnoux, D.; George, F.; Sampol, José; Raoult, Didier

doi:10.1128/iai.60.10.4388-4393.1992

Cited by 53 publications

(16 citation statements)

References 30 publications

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“…von Willebrand factor release, decreased thrombomodulin expression, and transient increases in TF expression have also been demonstrated in R conorii-infected endothelial cells. 48 This study reports that cultured vascular endothelial cells infected with R rickettsii rapidly and transiently express TF.…”

Section: Discussionmentioning

confidence: 93%

Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Sporn

Haidaris

Shi

et al. 1994

Blood

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Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.

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Section: Discussionmentioning

confidence: 93%

Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Sporn

Haidaris

Shi

et al. 1994

Blood

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“…Rickettsia rickettsii, an obligate, intracellular, and gram-negative bacterium, results in the expression of a proinflammatory and procoagulant cellular phenotype characterized by the induction of tissue factor (TF; factor III, thromboplastin) (33,39), E-selectin (32), interleukin-1␣ (IL-1␣) (34), and plasminogen activator inhibitor-1 (8,27). Since the endothelial cell is the primary target of infection, these alterations likely contribute significantly to the vascular pathology associated with the human rickettsial disease, Rocky Mountain spotted fever.…”

Section: Infection Of Cultured Vascular Endothelial Cells (Ec) Withmentioning

confidence: 99%

Involvement of Protein Kinase C inRickettsia rickettsii-Induced Transcriptional Activation of the Host Endothelial Cell

et al. 1999

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Our laboratory has reported on a biphasic pattern of nuclear factor κB (NF-κB) activation in cultured human umbilical vein endothelial cells during infection with Rickettsia rickettsii, an obligate, intracellular bacterium, and the etiologic agent of Rocky Mountain spotted fever. Transcriptional activation of the tissue factor (TF) gene during this infection has been shown to involve NF-κB. To further understand the signal transduction events underlying these phenomena, we studied the role of protein kinase C (PKC), a ubiquitous family of phospholipid-dependent enzymes implicated in the regulation of a variety of cell signaling pathways. Two inhibitors of PKC, namely, bisindolylmaleimide I hydrochloride (BM-1) and calphostin C, which exhibit different inhibitory properties towards various isozymes of PKC, were used. Infection of cells with R. rickettsii in the presence of BM-1 (50 nM) did not significantly affect NF-κB, whereas calphostin C (2.5 μM) completely blocked the early phase of NF-κB activation. The late, sustained phase also was not affected by treatment with BM-1. Downregulation of phorbol ester-sensitive PKCs by long-term treatment with phorbol 12-myristate 13-acetate (PMA) did not inhibit NF-κB activation. Likewise, this downregulation had no effect on induction of TF activity. The activity of TF was, however, sensitive to BM-1 and calphostin C, whereas expression of TF mRNA was inhibited only by calphostin C. Overall, these results suggest the lack of involvement of classical PKC pathways in R. rickettsii-induced NF-κB activation but the possible involvement of a non-PMA-responsive PKC isoform in the posttranscriptional control of TF expression.

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“…Considerable experimental evidence exists to support the notion that in addition to necrotic cell injury, the R. rickettsiiinfected EC alters its production of several proteins which likely results in presentation of a procoagulant and proinflammatory phenotype. Evidence for such responses is provided by studies of cultured EC, in which rickettsial infection cause increased expression of tissue factor (TF) (33,36), plasminogen activator inhibitor 1 (9,27), E-selectin (31), interleukin-1 (IL-1) (14,36), and IL-6 and -8 (14).…”

mentioning

confidence: 99%

Transcriptional Regulation of Endothelial Cell Tissue Factor Expression during Rickettsia rickettsii Infection: Involvement of the Transcription Factor NF-κB

et al. 1998

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The vascular endothelial cell (EC) is a primary target of infection with Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever. Changes in gene transcription elicited by intracellular infection, including EC expression of the coagulation pathway initiator known as tissue factor (TF), may contribute to the vascular pathology observed during disease. Nuclear run-on analysis of uninfected and infected, cultured human endothelial cells revealed that the rate of TF mRNA transcription is enhanced more than twofold at 3 h following infection, thus coinciding with increased steady-state levels of TF mRNA. TF mRNA remained relatively unstable during infection, with a half-life of 1.6 h. The eukaryotic protein synthesis inhibitor cycloheximide did not block R. rickettsii-induced increase in TF mRNA levels and actually resulted in its superinduction, thus revealing that de novo synthesis of host cell protein was not prerequisite to this transcriptional response. Involvement of the transcription factor NF-κB in R. rickettsii-induced TF expression was demonstrated by using two unrelated inhibitors of NF-κB activation. The antioxidant pyrrolidinedithiocarbamate and the proteasome inhibitorN-tosyl-l-phenylalanine chloromethyl ketone blocked expression of TF mRNA and activity during infection. This study demonstrates that R. rickettsii infection results in transcriptional activation of the TF gene and that this response involves activation of the transcription factor NF-κB.

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von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells

Cited by 53 publications

References 30 publications

Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Involvement of Protein Kinase C inRickettsia rickettsii-Induced Transcriptional Activation of the Host Endothelial Cell

Transcriptional Regulation of Endothelial Cell Tissue Factor Expression during Rickettsia rickettsii Infection: Involvement of the Transcription Factor NF-κB

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