Post-transcriptional regulation of endothelial cell plasminogen activator inhibitor-1 expression during R. rickettsii infection

Shi, Rui-Jin; Simpson-Haidaris, Patricia J.; Marder, Victor J.; Silverman, David J.; Sporn, Lee Ann

doi:10.1006/mpat.1999.0333

Cited by 14 publications

(9 citation statements)

References 36 publications

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“…Whereas a decline in COX-2 transcription between 7 and 14 h postinfection correlates well with the kinetics of p38 phosphorylation, more instability due to multiple copies of Shaw-Kamen pentamer AUUUA repeats in the 3Ј-untranslated region may also contribute to the disappearance of COX-2 mRNA (2, 36). The possibility that the regulation of COX-2 expression during Rickettsia infection of endothelial cells involves posttranscriptional control mechanisms, a precedent of which was reported earlier for plasminogen activator inhibitor 1 expression in R. rickettsii-infected host cells (38), is the subject of further detailed investigation in our laboratory. Furthermore, higher levels of protein in cells infected for 6 and 12 h likely reflect the time delay between promoter activation, leading to enhanced transcription early during the infection, and subsequent synthesis of bioactive protein, as reported to occur during endothelial cell responses to hypoxia (35), activated protein C (6), and other physiological mediators (54).…”

Section: Discussionmentioning

confidence: 66%

“…Human umbilical vein EC, an established model cell type that has been used to investigate in vitro rickettsiaendothelium interactions (39) and a number of different host cell responses (8,9,13,15,22,30,32,34,(37)(38)(39)(40)(41)(42), were isolated from freshly collected umbilical cords by collagenase digestion and then seeded on gelatin (2% [wt/vol])-coated cell culture plates as described previously (33). Primary cultures were allowed to grow to confluence in McCoy's medium supplemented with 20% fetal bovine serum, heparin (100 g/ml), and endothelial cell growth supplement (50 g/ml), at which point they were routinely split at a ratio of 1:3.…”

Section: Methodsmentioning

confidence: 99%

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Infection of Human Endothelial Cells with Spotted Fever Group Rickettsiae Stimulates Cyclooxygenase 2 Expression and Release of Vasoactive Prostaglandins

Rydkina¹,

Sahni²,

Baggs

et al. 2006

Infect Immun

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Rickettsiae, a diverse group of obligately intracellular gram-negative bacteria, include etiologic agents of the spotted fever and typhus groups of diseases. Rocky Mountain spotted fever and boutonneuse fever, due to Rickettsia rickettsii and R. conorii, respectively, are characterized by widespread infection of the vascular endothelium, microvascular injury, and vasculitis. Cultured human endothelial cells (EC) are highly susceptible to infection and respond by altering the expression of adhesion molecules, regulatory cytokines, and the antioxidant enzyme heme oxygenase (HO). In the vasculature, HO regulates the cyclooxygenase (COX) enzymes, among which the inducible isozyme COX-2 facilitates the synthesis of prostaglandins (PGs). Using in vitro and ex vivo models of infection, we demonstrate here that R. rickettsii infection of human EC causes robust induction of COX-2 mRNA and protein expression but has no apparent effect on the constitutive COX-1 isoform. Cells infected with viable rickettsiae consistently displayed significantly increased secretion of 6-keto-PGF 1␣ and PGE 2 . R. rickettsii-induced COX-2 was sensitive to inhibitors of de novo transcription and the pyridinylimidazole-based compound SB 203580, suggesting that this transcriptional host cell response involves signaling through p38 mitogen-activated protein kinase. PG production by infected cells was abrogated by NS 398 (a selective COX-2 inhibitor) and indomethacin (a pan-COX inhibitor). Immunohistochemical staining of sections of infected umbilical cords and corresponding uninfected controls revealed comparatively more intense and abundant staining for COX-2 in infected endothelia. Induction of the endothelial COX-2 system and the resultant enhanced release of vasoactive PGs may contribute to the regulation of inflammatory responses and vascular permeability changes during spotted fever rickettsioses.Pathogenic species of the genus Rickettsia include gramnegative bacteria capable of causing mild to severe diseases in humans. Spotted fever group (SFG) organisms, which represent one of the two major groups of rickettsiae, are found globally in their characteristic arthropod vectors and are often classified to reflect the location of their predominant geographic distribution, for example, Rickettsia sibirica and R. australis, or the resultant human disease, such as Rocky Mountain spotted fever and Mediterranean spotted fever, caused by R. rickettsii and R. conorii, respectively (27, 47). Rocky Mountain spotted fever is a life-threatening illness and can be fatal in children, the elderly, and immunodeficient individuals if there is a lack of early detection and timely intervention with suitable antibiotic therapy. Yet another recently realized and alarming epidemiologic aspect of this disease is that tick-to-human transmission can occur not only through the previously identified principal vectors of Dermacentor species, but also through the more commonly distributed brown dog tick, Rhipicephalus sanguineus, suggesting the capability of this obliga...

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Section: Discussionmentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Infection of Human Endothelial Cells with Spotted Fever Group Rickettsiae Stimulates Cyclooxygenase 2 Expression and Release of Vasoactive Prostaglandins

Rydkina¹,

Sahni²,

Baggs

et al. 2006

Infect Immun

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“…This was soon followed by a series of findings that ECs are not simply injured by infection, but also launch distinct cellular responses including functional changes indicative of an activated phenotype – a phenomenon referred to as ‘endothelial activation’. Specifically, in vitro endothelial responses to R. rickettsii and R. conorii include changes in the surface adhesiveness for platelets [36]; increased expression of tissue factor [37,38], IL-1α [39,40], intercellular and vascular cell-adhesion molecules [41], and E-selectin [42]; increased synthesis of plasminogen activator inhibitor-1 [43,44]; and release of von Willebrand factor from Weibel–Palade bodies [37,45]. In addition, infection with the TG species R. prowazekii results in enhanced secretion of the arachidonate-derived autocoids PGE 2 and PGI 2 [46].…”

Section: Rickettsial Interactions With Host Cells In Vitro: Activatiomentioning

confidence: 99%

Host-Cell Interactions with Pathogenic Rickettsia Species

2009

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Pathogenic Rickettsia species are Gram-negative, obligate intracellular bacteria responsible for the spotted fever and typhus groups of diseases around the world. It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of the pathogen's affinity for endothelium lining the blood vessels, the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability, collectively termed ‘Rickettsial vasculitis’. Signaling mechanisms leading to transcriptional activation of target cells in response to Rickettsial adhesion and/or invasion, differential activation of host-cell signaling due to infection with spotted fever versus typhus subgroups of Rickettsiae, and their contributions to the host's immune responses and determination of cell fate are the major subtopics of this review. Also included is a succinct analysis of established in vivo models and their use for understanding Rickettsial interactions with host cells and pathogenesis of vasculotropic rickettsioses. Continued progress in these important but relatively under-explored areas of bacterial pathogenesis research should further highlight unique aspects of Rickettsial interactions with host cells, elucidate the biological basis of endothelial tropism and reveal novel chemotherapeutic and vaccination strategies for debilitating Rickettsial diseases.

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“…Thep rotein binding to this element have beeni solated and termed PA I-RNA binding protein 1(PA I-RBP1) (227,228) butt he role of PA I-RBP1 in PA I-1 regulation hasy et to be defined. Anumber of other agents have beenshown to influence PA I-1 mRNAt urnover, includingo steogenic protein-1 (229), angiotensin II (230,231), and Rickettsia rickettsii infection (232).…”

Section: Upar Mrnamentioning

confidence: 99%

Transcriptional and posttranscriptional regulation of the plasminogen activator system

Nagamine¹,

Medcalf²,

Muñoz‐Cánoves³

2005

Thromb Haemost

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SummaryThecoreprotein components of the plasminogenactivator (PA) system aret wo plasminogen activators, twop lasminogen activator inhibitorsand aurokinasetype plasminogenactivator-specific cell surfacer eceptor.Varioustypesofbiologicalr egulation areexerted through the interplayofthese components mutually and with extracellular matrix proteins and cell membrane proteins, with or without involving proteolytic activity.Reflecting these diverse biologicalroles, thelevel and activityofeach componento ft he PA system is under the control of av ariety of Keywords Review, plasminogen activator,generegulation,mRNA stability regulatorym echanisms. Thee xpression levelo fap rotein reflects the levelofthe corresponding mRNA, which is essentially the netresult of de novo synthesis,i.e.transcription, and degradation. Manyr ecents tudiesh aves hown thatt he regulation of mRNA stabilityisdynamic and cell specific.Accordingly, we are learning that the mRNAsofthe PA system arealsothe subject of diverse regulatorymechanisms. In this shortreview, we summarize current understanding of the transcriptionaland mRNAstabilityregulationofthe PA system.

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Post-transcriptional regulation of endothelial cell plasminogen activator inhibitor-1 expression during R. rickettsii infection

Cited by 14 publications

References 36 publications

Infection of Human Endothelial Cells with Spotted Fever Group Rickettsiae Stimulates Cyclooxygenase 2 Expression and Release of Vasoactive Prostaglandins

Infection of Human Endothelial Cells with Spotted Fever Group Rickettsiae Stimulates Cyclooxygenase 2 Expression and Release of Vasoactive Prostaglandins

Host-Cell Interactions with Pathogenic Rickettsia Species

Transcriptional and posttranscriptional regulation of the plasminogen activator system

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