Interleukin-1 alpha production during Rickettsia rickettsii infection of cultured endothelial cells: potential role in autocrine cell stimulation

Sporn, Lee Ann; Marder, Victor J.

doi:10.1128/iai.64.5.1609-1613.1996

Cited by 59 publications

(26 citation statements)

References 43 publications

(21 reference statements)

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“…Rickettsiae are among the few microorganisms that infect mainly endothelial cells. As a consequence of rickettsial infection, these cells express an inflammatory phenotype which includes cytokines such as IL-1␣, IL-6, and IL-8, 27,28 and adhesion molecules including ICAM-1, VCAM-1, 29 and endothelialleukocyte adhesion molecule 1. 30 Our results led us to hypothesize that antigenic presentation by endothelial cells in the context of increased expression of inflammatory adhesion molecules might be sufficient to trigger the effector mechanisms of anti-rickettsial T cells and in this way may bypass the requirement for chemokines.…”

Section: Discussionmentioning

confidence: 99%

Effect of Blocking the Cxcl9/10-Cxcr3 Chemokine System in the Outcome of Endothelial-Target Rickettsial Infections

Valbuena

Walker

2004

The American Journal of Tropical Medicine and Hygiene

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Rickettsiae cause systemic infections such as Rocky Mountain spotted fever and boutonneuse fever. The main cellular target of these obligately intracellular bacteria is the endothelium. T lymphocytes are the most important effectors of immunity, and the CXCR3 ligands CXCL9 and CXCL10 may play an important role in the T cell-mediated clearance of rickettsiae from the infected vasculature as suggested by recent expression studies. Here we showed that antibody-mediated neutralization of CXCL9 and CXCL10, and CXCR3 gene knockout, had no effect on survival or bacterial loads of mice infected with rickettsiae. We also demonstrated that rickettsiae triggered the endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 in vivo. These findings suggested that antigenic presentation by endothelial cells together with an endothelial inflammatory phenotype induced by the rickettsial infection may be sufficient to arrest T cells and trigger their anti-rickettsial effector mechanisms without the need for chemokines.

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Section: Discussionmentioning

confidence: 99%

Effect of Blocking the Cxcl9/10-Cxcr3 Chemokine System in the Outcome of Endothelial-Target Rickettsial Infections

Valbuena

Walker

2004

The American Journal of Tropical Medicine and Hygiene

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“…Chlamydia pneumoniae, which has recently been linked to coronary heart disease, has been demonstrated to cause an upregulation of E-selectin, intercellular adhesion molecule (ICAM-1), and vascular cell adhesion molecule (VCAM-1) (13). Rickettsia rickettsii infection of EC stimulates these cells to produce interleukin-1␣ (IL-1␣) (29). Rickettsia conorii infection of EC has also been demonstrated to enhance the expression of the adhesive molecules E-selectin, ICAM-1, and VCAM-1 (7).…”

Section: Discussionmentioning

confidence: 99%

Invasion of Aortic and Heart Endothelial Cells by Porphyromonas gingivalis

1998

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Invasion of host cells is believed to be an important strategy utilized by a number of pathogens, which affords them protection from the host immune system. The connective tissues of the periodontium are extremely well vascularized, which allows invading microorganisms, such as the periodontal pathogen Porphyromonas gingivalis, to readily enter the bloodstream. However, the ability of P. gingivalis to actively invade endothelial cells has not been previously examined. In this study, we demonstrate that P. gingivalis can invade bovine and human endothelial cells as assessed by an antibiotic protection assay and by transmission and scanning electron microscopy. P. gingivalis A7436 was demonstrated to adhere to and to invade fetal bovine heart endothelial cells (FBHEC), bovine aortic endothelial cells (BAEC), and human umbilical vein endothelial cells (HUVEC). Invasion efficiencies of 0.1, 0.2, and 0.3% were obtained with BAEC, HUVEC, and FBHEC, respectively. Invasion of FBHEC and BAEC by P. gingivalis A7436 assessed by electron microscopy revealed the formation of microvillus-like extensions around adherent bacteria followed by the engulfment of the pathogen within vacuoles. Invasion of BAEC by P. gingivalisA7436 was inhibited by cytochalasin D, nocodazole, staurosporine, protease inhibitors, and sodium azide, indicating that cytoskeletal rearrangements, protein phosphorylation, energy metabolism, andP. gingivalis proteases are essential for invasion. In contrast, addition of rifampin, nalidixic acid, and chloramphenicol had little effect on invasion, indicating that bacterial RNA, DNA, and de novo protein synthesis are not required for P. gingivalisinvasion of endothelial cells. Likewise de novo protein synthesis by endothelial cells was not required for invasion by P. gingivalis. P. gingivalis 381 was demonstrated to adhere to and to invade BAEC (0.11 and 0.1% efficiency, respectively). However, adherence and invasion of the corresponding fimA mutant DPG3, which lacks the major fimbriae, was not detected. These results indicate thatP. gingivalis can actively invade endothelial cells and that fimbriae are required for this process. P. gingivalisinvasion of endothelial cells may represent another strategy utilized by this pathogen to thwart the host immune response.

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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%

“…Except for an apparent requirement for intracellular infection (33), the mechanisms governing R. rickettsii-induced TF expression, as well as expression of other rickettsia-induced proteins, have remained elusive. Endothelial TF expression, which is induced in cultured EC in response to soluble agonists such as cytokines (5,6,18), lipopolysaccharides (LPSs) (7), and phorbol esters (16), is controlled by transcriptional and posttranscriptional control mechanisms (1,8,10,26).…”

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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Interleukin-1 alpha production during Rickettsia rickettsii infection of cultured endothelial cells: potential role in autocrine cell stimulation

Abstract: Rickettsia rickettsii infection results in numerous responses by cultured endothelial cells, among them a rapid, transient increase in steady-state levels of tissue factor mRNA (L. A.

Cited by 59 publications

References 43 publications

Effect of Blocking the Cxcl9/10-Cxcr3 Chemokine System in the Outcome of Endothelial-Target Rickettsial Infections

Effect of Blocking the Cxcl9/10-Cxcr3 Chemokine System in the Outcome of Endothelial-Target Rickettsial Infections

Invasion of Aortic and Heart Endothelial Cells by Porphyromonas gingivalis

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

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