<i>Rickettsia rickettsii</i>Infection of Cultured Human Endothelial Cells Induces Heme Oxygenase 1 Expression

Rydkina, Elena; Sahni, Abha; Silverman, David J.; Sahni, Sanjeev K.

doi:10.1128/iai.70.8.4045-4052.2002

Cited by 35 publications

(47 citation statements)

References 67 publications

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“…In addition, the kinetics and intensities of induced HO-1 mRNA expression activation during 24 h of infection were almost identical among these specialized endothelial cell types ( Fig. 4A and B) and quite similar to those reported earlier for infected HUVECs (22). All ECs had a peak of HO-1 mRNA expression, predominantly at 3 to 7 h pi, with the exception of HPAECs, where this response was delayed to 14 h. Intriguingly, HMECs and SVHCECs demonstrated the highest level of HO-1 mRNA expression of about 4.5-and 3.8-fold in comparison with uninfected control, whereas HPMECs were least responsive, with about 2.2-fold induction (Fig.…”

Section: R Rickettsii Infection Of Different Types Of Endothelial Cesupporting

confidence: 69%

“…Equal amounts of RNA isolated from infected ECs and corresponding uninfected cells (controls) using TRI-reagent protocol were subjected to Northern blot analysis using radioactively labeled cDNA probes designed for specific detection of cyclooxygenase 2 (COX-2) (Cayman Chemical) and HO-1 transcripts (22,24). The differences in sample loading on different lanes were corrected by stripping of the signals and reprobing for the GAPDH (glyceraldehyde-3-phosphate dehydrogenase) housekeeping gene.…”

Section: Methodsmentioning

confidence: 99%

“…Importantly, cultured HUVECs used in these studies were found to retain many characteristic features of capillary vascular endothelium such as the presence of Weibel-Palade bodies and positive staining for factor VIII antigen on the cell surface (30, 31). Subsequent experimental findings using this in vitro model of infection have since established that endothelial cells infected with R. rickettsii launch an antioxidant response via increased expression of heme oxygenase 1 (HO-1) to combat the oxidative stress due to increased accumulation of intracellular peroxides and oxygen free radicals (11,22,28). Endothelial cell activation in response to R. rickettsii and Rickettsia conorii involves the activation of nuclear factor kappa B (NF-B) and p38 mitogen-activated protein (MAP) kinase signaling and is characterized by altered expression/secretion profile of various cytokines and chemokines including interleukin-1␣ (IL-1␣), IL-8, monocyte chemoattractant protein 1 (MCP-1), Mig, and IP-10 (7, 16, 23, 33, 35).…”

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confidence: 99%

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Rickettsia rickettsiiInfection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms

2010

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Although inflammation and altered barrier functions of the vasculature, due predominantly to the infection of endothelial cell lining of small and medium-sized blood vessels, represent salient pathological features of human rickettsioses, the interactions between pathogenic rickettsiae and microvascular endothelial cells remain poorly understood. We have investigated the activation of nuclear transcription factor-kappa B (NF-B) and p38 mitogen-activated protein (MAP) kinase, expression of heme oxygenase 1 (HO-1) and cyclooxygenase 2 (COX-2), and secretion of chemokines and prostaglandins after Rickettsia rickettsii infection of human cerebral, dermal, and pulmonary microvascular endothelial cells in comparison with pulmonary artery cells of macrovascular origin. NF-B and p38 kinase activation and increased HO-1 mRNA expression were clearly evident in all cell types, along with relatively similar susceptibility to R. rickettsii infection in vitro but considerable variations in the intensities/kinetics of the aforementioned host responses. As expected, the overall activation profiles of macrovascular endothelial cells derived from human pulmonary artery and umbilical vein were nearly identical. Interestingly, cerebral endothelial cells displayed a marked refractoriness in chemokine production and secretion, while all other cell types secreted various levels of interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to infection. A unique feature of all microvascular endothelial cells was the lack of induced COX-2 expression and resultant inability to secrete prostaglandin E 2 after R. rickettsii infection. Comparative evaluation thus yields the first experimental evidence for the activation of both common and unique cell type-specific host response mechanisms in macrovascular and microvascular endothelial cells infected with R. rickettsii, a prototypical species known to cause Rocky Mountain spotted fever in humans.The obligately intracellular Alphaproteobacteria belonging to genus Rickettsia are now classified into four subgroups, which include an ancestral group and a transitional group in addition to two major antigenically defined groups comprised of spotted fever and typhus species (12). Pathogenic rickettsiae display tropism for vascular endothelial cell lining of small and mediumsized blood vessels in their mammalian hosts. As a consequence, the predominant pathological features of resultant clinical syndromes-for example, Rocky Mountain spotted fever due to Rickettsia rickettsii-are generally attributed to altered vascular functions due to preferential infection of the endothelium (27, 36). However, despite critical contributions of endothelial injury, inflammation, and dysfunction to the pathogenesis of vasculotropic rickettsioses, the biological basis of rickettsial interactions with microvascular endothelium of vertebrate hosts still remains poorly understood.An initial breakthrough in the laboratory investigations of the interplay between host cells and pathogenic rickettsiae wa...

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Section: R Rickettsii Infection Of Different Types Of Endothelial Cesupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Rickettsia rickettsiiInfection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms

2010

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“…Infections by influenza virus, 61 encephalomyocarditis virus, 62 Listeria monocytogenes, 63 and Rickettsia rickettsii 64 all show significant up-regulation of HO-1, suggesting that this enzyme may participate in cellular responses to some intracellular pathogens. We have assessed the expression of HO-1 in our DMVEC system following infection with the KSHV-related rhesus rhadinovirus (RRV).…”

Section: Discussionmentioning

confidence: 99%

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

McAllister

Hansen

Ruhl

et al. 2004

Blood

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IntroductionKaposi sarcoma-associated herpesvirus (KSHV; also human herpesvirus-8) is implicated in all clinical forms of KS 1,2 as well as the lymphoproliferative disorders primary effusion lymphoma (PEL) 3,4 and multicentric Castleman disease (MCD). 5 Endothelial cells harbor the KSHV genome in vivo, 1,6,7 are permissive for virus infection in vitro, [8][9][10][11] and are thought to be the precursors of spindle cells. [12][13][14][15] We and others have shown that in vitro infection of human dermal microvascular endothelial cells (DMVECs) with KSHV induces a spindle cell morphology and characteristics of a transformed phenotype, including loss of contact inhibition and growth in soft agar. [8][9][10][11] Because explanted KS cells fail to maintain the KSHV genome following serial passage, 16,17 in vitro infection of DMVECs has proved to be an invaluable tool for the study of KSHV pathogenic mechanisms. 18,19 KSHV, like other herpesviruses, has a substantial coding capacity that includes viral genes unique to this human pathogen, genes that share homology with other members of the herpesviridae, as well as genes that appear to have originated in the host genome. 20,21 Of note, at least 3 of these gene products, vFLIP (viral Fas-associating protein with death domain-like interleukin-1␤ [IL-1␤]-converting enzyme [FLICE]-inhibitory protein), viral cyclin (vCYC), and latency-associated nuclear antigen (LANA), are believed to comprise the viral latency expression program and are consistently expressed in all virally infected cells in KS, PEL, and MCD. [22][23][24] The gene product of open reading frame 71 (ORF 71), vFLIP, is thought to play an important role in prevention of apoptotic cell death. 25 The activity of a homolog of cellular cyclin D, vCYC (ORF 72), 26 together with the modulation of cellular transcription wrought by LANA (ORF 73) 27 is thought to be involved in KSHV-induced host cell transformation. Additionally, LANA is indispensable for maintenance of the viral genome. 28 Other gene products, such as viral G-protein-coupled receptor (vGCR) 29,31 are classified as lytic gene products and are expressed in only a minority of cells in vivo. [32][33][34] Although reactivation of KSHV from the latent state and subsequent completion of the viral lytic expression cascade is incompatible with survival of a host cell, lytic gene products are thought to have paracrine influences on both latently infected and uninfected cells and are thus considered vital for lesion development. 35 We have used our previously described in vitro KS model to dissect viral mechanisms of pathogenesis. 18,19 The salient features of our model include recapitulation of KS cell physiology, including spindle cell formation, loss of contact inhibition, and anchoragedependent growth restriction; long-term propagation of predominantly latently infected cells; and the ability to generate ageand passage-matched KSHV-infected and uninfected cultures. 11 This system has been amenable to gene expression profiling by cDNA microarrays and has ...

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“…Prostaglandins and leukotrienes are generated from arachidonic acid by the cyclooxygenase (COX) enzymes, which are controlled by heme oxygenase (HO-1) [Haider et al, 2002;Rydkina et al, 2002]. In vitro and in vivo studies of rickettsial infection have shown that increased COX-2 expression in endothelial cells is related to increased prostaglandin secretion, which may explain some of the clinical manifestations of rickettsioses, such as pain, fever and inflammation.…”

Section: Endothelium and Pathophysiology Of Rickettsiosesmentioning

confidence: 99%

Vasculitis: Endothelial Dysfunction During Rickettsial Infection

Bechah¹,

Capo²,

Mège³

2011

Advances in the Etiology, Pathogenesis and Pathology of Vasculitis

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Rickettsia rickettsiiInfection of Cultured Human Endothelial Cells Induces Heme Oxygenase 1 Expression

Cited by 35 publications

References 67 publications

Rickettsia rickettsiiInfection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms

Rickettsia rickettsiiInfection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

Vasculitis: Endothelial Dysfunction During Rickettsial Infection

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