Sander Ouburg | VU University Medical Center (original) (raw)

Papers by Sander Ouburg

Research paper thumbnail of Alarmingly poor performance in Chlamydia trachomatis point-of-care testing

Sexually transmitted infections, 2010

Infection by Chlamydia trachomatis (CT) is the most prevalent sexually transmitted infection (STI... more Infection by Chlamydia trachomatis (CT) is the most prevalent sexually transmitted infection (STI) world wide. The most frequently used diagnostic test for CT is a nucleic acid amplification test (NAAT), which is highly sensitive and specific. To further shorten time delay until diagnosis has been made, in order to prevent CT spread, the use of point-of-care (POC) tests may be the way forward.

Research paper thumbnail of NOD1 in contrast to NOD2 functional polymorphism influence Chlamydia trachomatis infection and the risk of tubal factor infertility

Pathogens and disease, 2015

Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structura... more Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structural units of bacterial walls. Recognition triggers specific immune signalling pathways and leads to pro-inflammatory cytokine upregulation and adequate immune response. We investigated whether two functional polymorphisms in NOD1 and NOD2 exert an effect on susceptibility to (STD patients) and severity of (female patients visiting the fertility clinic) Chlamydia trachomatis infection in 807 Dutch Caucasian women. A significant association of the NOD1 +32656 GG insertion variant with protection against infection with C. trachomatis has been detected [p: 0.0057; OR: 0.52]. When comparing C. trachomatis-positive women without symptoms to C. trachomatis-positive women with symptoms, and to C. trachomatis-positive women with TFI, we observed an increasing trend in carriage of the GG allele [Ptrend: 0.0003]. NOD2 1007fs failed to reveal an association. We hypothesize that the underlying mechanis...

Research paper thumbnail of Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 2005

T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydi... more T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a func...

Research paper thumbnail of Translational Potential into Health Care of Basic Genomic and Genetic Findings for Human Immunodeficiency Virus, Chlamydia trachomatis , and Human Papilloma Virus

BioMed Research International, 2013

Individual variations in susceptibility to an infection as well as in the clinical course of the ... more Individual variations in susceptibility to an infection as well as in the clinical course of the infection can be explained by pathogen related factors, environmental factors, and host genetic differences. In this paper we review the state-of-the-art basic host genomic and genetic findings' translational potential of human immunodeficiency virus (HIV), Chlamydia trachomatis (CT), and Human Papilloma Virus (HPV) into applications in public health, especially in diagnosis, treatment, and prevention of complications of these infectious diseases. There is a significant amount of knowledge about genetic variants having a positive or negative influence on the course and outcome of HIV infection. In the field of Chlamydia trachomatis, genomic advances hold the promise of a more accurate subfertility prediction test based on single nucleotide polymorphisms (SNPs). In HPV research, recent developments in early diagnosis of infection-induced cervical cancer are based on methylation tests. Indeed, triage based on methylation markers might be a step forward in a more effective stratification of women at risk for cervical cancer. Our review found an imbalance between the number of host genetic variants with a role in modulating the immune response and the number of practical genomic applications developed thanks to this knowledge.

Research paper thumbnail of Lymphogranuloma venereum diagnostics: from culture to real-time quadriplex polymerase chain reaction

Sexually Transmitted Infections, 2008

84;252-253 Sex. Transm. Inf. Servaas A Morré, Sander Ouburg, Michiel A van Agtmael and Henry J C ... more 84;252-253 Sex. Transm. Inf. Servaas A Morré, Sander Ouburg, Michiel A van Agtmael and Henry J C de Vries reaction culture to real-time quadriplex polymerase chain Lymphogranuloma venereum diagnostics: from http://sti.bmj.com/cgi/content/full/84/4/252

Research paper thumbnail of Analysis of multiple single nucleotide polymorphisms (SNP) on DNA traces from plasma and dried blood samples

Journal of Immunological Methods, 2007

Reliable analysis of single nucleotide polymorphisms (SNPs) in DNA derived from samples containin... more Reliable analysis of single nucleotide polymorphisms (SNPs) in DNA derived from samples containing low numbers of cells or from suboptimal sources can be difficult. A new procedure to characterize multiple SNPs in traces of DNA from plasma and old dried blood samples was developed. Six SNPs in the Mannose Binding Lectin 2 (MBL2) gene were chosen as targets for analysis.

Research paper thumbnail of Single Nucleotide Polymorphisms in TLR9 Are Highly Associated with Susceptibility to Bacterial Meningitis in Children

Clinical Infectious Diseases, 2011

Background. Bacterial meningitis (BM) is a severe infection mainly caused by Streptococcus pneumo... more Background. Bacterial meningitis (BM) is a severe infection mainly caused by Streptococcus pneumoniae and Neisseria meningitidis (NM). However, genetically determined susceptibility to develop severe infections by these microorganisms is variable between individuals. Toll-like receptor 9 (TLR9) recognizes bacterial DNA leading to intracellular inflammatory signaling. Single nucleotide polymorphisms (SNPs) within the TLR9 gene are associated with susceptibility to several diseases, no such association with meningitis has been described.

Research paper thumbnail of Serovar D and E of serogroup B induce highest serological responses in urogenital Chlamydia trachomatis infections

BMC Infectious Diseases, 2014

Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) worldw... more Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) worldwide. A strong link between C. trachomatis serogroup/serovar and serological response has been suggested in a previous preliminary study. The aim of the current study was to confirm and strengthen those findings about serological IgG responses in relation to C. trachomatis serogroups and serovars.

Research paper thumbnail of A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections

European journal of gastroenterology & hepatology, 2005

This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in w... more This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfor...

Research paper thumbnail of Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection

PLoS ONE, 2012

Background: Regulation of immune responses is critical for controlling inflammation and disruptio... more Background: Regulation of immune responses is critical for controlling inflammation and disruption of this process can lead to tissue damage. We reported that CXCL13 was induced in fallopian tube tissue following C. trachomatis infection. Here, we examined the influence of the CXCL13-CXCR5 axis in chlamydial genital infection.

Research paper thumbnail of The true ligand of the NOD2 receptor is peptidoglycan instead of lipopolysaccharide: A schematic representation of ligand-receptor interactions and NF-κB activation

Gastroenterology, 2004

Reply. I thank Danese et al. for their comments about our editorial on the induction of matrix me... more Reply. I thank Danese et al. for their comments about our editorial on the induction of matrix metalloproteinase-9 (MMP-9) expression by Helicobacter pylori infection. 1 They report in their letter that MMP-9 expression has been reduced after H. pylori eradication both in epithelial cells and in mucosal fibroblasts. I acknowledge that their data confirm my findings and support my conclusions. I read with interest the data from this eradication study. They report no change of MMP-9 expression after eradication in macrophages. I observed no association between MMP-9 expression and H. pylori infection in macrophages in gastric ulcers. 1 These results suggest distinct mechanism of MMP-9 expression between epithelial cells and fibroblasts, and macrophages. MMP-9 expression in epithelial cells and fibroblasts is dependent on H. pylori infection, whereas in macrophages it is independent of H. pylori infection. The increase of MMP-9 in macrophages may be causally linked to the mucosal injury. The plasma levels of MMP-9 in patients with gastric cancer were significantly higher than those in healthy individuals. 2 It is possible that the plasma levels of MMP-9 are increased in patients with H. pyloriassociated gastritis and gastric ulcer. I am under investigation the plasma levels of MMP-9 in these patients.

Research paper thumbnail of The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology

The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the t... more The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women.

Research paper thumbnail of Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

Background: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal t... more Background: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components.

Research paper thumbnail of TRAIL-R1 is a negative regulator of pro-inflammatory responses and modulates long-term sequelae resulting from Chlamydia trachomatis infections in humans

PloS one, 2014

The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncon... more The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncontrolled inflammation can enhance pathology. In mice, TNF-related apoptosis-inducing ligand receptor (TRAIL-R), known for its effects on apoptosis, also regulates inflammation. In humans, the four homologues of TRAIL-R had never been investigated for effects on inflammation. Here, we examined whether TRAIL-R regulates inflammation during chlamydial infection. We examined TRAIL-R1 single nucleotide polymorphisms (SNPs) in an Ecuadorian cohort with and without C. trachomatis infections. There was a highly significant association for the TRAIL+626 homozygous mutant GG for infection vs no infection in this population. To confirm the results observed in the human population, primary lung fibroblasts and bone marrow-derived macrophages (BMDMs) were isolated from wildtype (WT) and TRAIL-R-deficient mice, and TRAIL-R1 levels in human cervical epithelial cells were depleted by RNA interference. In...

Research paper thumbnail of Alarmingly poor performance in Chlamydia trachomatis point-of-care testing

Sexually transmitted infections, 2010

Infection by Chlamydia trachomatis (CT) is the most prevalent sexually transmitted infection (STI... more Infection by Chlamydia trachomatis (CT) is the most prevalent sexually transmitted infection (STI) world wide. The most frequently used diagnostic test for CT is a nucleic acid amplification test (NAAT), which is highly sensitive and specific. To further shorten time delay until diagnosis has been made, in order to prevent CT spread, the use of point-of-care (POC) tests may be the way forward.

Research paper thumbnail of NOD1 in contrast to NOD2 functional polymorphism influence Chlamydia trachomatis infection and the risk of tubal factor infertility

Pathogens and disease, 2015

Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structura... more Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structural units of bacterial walls. Recognition triggers specific immune signalling pathways and leads to pro-inflammatory cytokine upregulation and adequate immune response. We investigated whether two functional polymorphisms in NOD1 and NOD2 exert an effect on susceptibility to (STD patients) and severity of (female patients visiting the fertility clinic) Chlamydia trachomatis infection in 807 Dutch Caucasian women. A significant association of the NOD1 +32656 GG insertion variant with protection against infection with C. trachomatis has been detected [p: 0.0057; OR: 0.52]. When comparing C. trachomatis-positive women without symptoms to C. trachomatis-positive women with symptoms, and to C. trachomatis-positive women with TFI, we observed an increasing trend in carriage of the GG allele [Ptrend: 0.0003]. NOD2 1007fs failed to reveal an association. We hypothesize that the underlying mechanis...

Research paper thumbnail of Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 2005

T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydi... more T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a func...

Research paper thumbnail of Translational Potential into Health Care of Basic Genomic and Genetic Findings for Human Immunodeficiency Virus, Chlamydia trachomatis , and Human Papilloma Virus

BioMed Research International, 2013

Individual variations in susceptibility to an infection as well as in the clinical course of the ... more Individual variations in susceptibility to an infection as well as in the clinical course of the infection can be explained by pathogen related factors, environmental factors, and host genetic differences. In this paper we review the state-of-the-art basic host genomic and genetic findings' translational potential of human immunodeficiency virus (HIV), Chlamydia trachomatis (CT), and Human Papilloma Virus (HPV) into applications in public health, especially in diagnosis, treatment, and prevention of complications of these infectious diseases. There is a significant amount of knowledge about genetic variants having a positive or negative influence on the course and outcome of HIV infection. In the field of Chlamydia trachomatis, genomic advances hold the promise of a more accurate subfertility prediction test based on single nucleotide polymorphisms (SNPs). In HPV research, recent developments in early diagnosis of infection-induced cervical cancer are based on methylation tests. Indeed, triage based on methylation markers might be a step forward in a more effective stratification of women at risk for cervical cancer. Our review found an imbalance between the number of host genetic variants with a role in modulating the immune response and the number of practical genomic applications developed thanks to this knowledge.

Research paper thumbnail of Lymphogranuloma venereum diagnostics: from culture to real-time quadriplex polymerase chain reaction

Sexually Transmitted Infections, 2008

84;252-253 Sex. Transm. Inf. Servaas A Morré, Sander Ouburg, Michiel A van Agtmael and Henry J C ... more 84;252-253 Sex. Transm. Inf. Servaas A Morré, Sander Ouburg, Michiel A van Agtmael and Henry J C de Vries reaction culture to real-time quadriplex polymerase chain Lymphogranuloma venereum diagnostics: from http://sti.bmj.com/cgi/content/full/84/4/252

Research paper thumbnail of Analysis of multiple single nucleotide polymorphisms (SNP) on DNA traces from plasma and dried blood samples

Journal of Immunological Methods, 2007

Reliable analysis of single nucleotide polymorphisms (SNPs) in DNA derived from samples containin... more Reliable analysis of single nucleotide polymorphisms (SNPs) in DNA derived from samples containing low numbers of cells or from suboptimal sources can be difficult. A new procedure to characterize multiple SNPs in traces of DNA from plasma and old dried blood samples was developed. Six SNPs in the Mannose Binding Lectin 2 (MBL2) gene were chosen as targets for analysis.

Research paper thumbnail of Single Nucleotide Polymorphisms in TLR9 Are Highly Associated with Susceptibility to Bacterial Meningitis in Children

Clinical Infectious Diseases, 2011

Background. Bacterial meningitis (BM) is a severe infection mainly caused by Streptococcus pneumo... more Background. Bacterial meningitis (BM) is a severe infection mainly caused by Streptococcus pneumoniae and Neisseria meningitidis (NM). However, genetically determined susceptibility to develop severe infections by these microorganisms is variable between individuals. Toll-like receptor 9 (TLR9) recognizes bacterial DNA leading to intracellular inflammatory signaling. Single nucleotide polymorphisms (SNPs) within the TLR9 gene are associated with susceptibility to several diseases, no such association with meningitis has been described.

Research paper thumbnail of Serovar D and E of serogroup B induce highest serological responses in urogenital Chlamydia trachomatis infections

BMC Infectious Diseases, 2014

Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) worldw... more Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) worldwide. A strong link between C. trachomatis serogroup/serovar and serological response has been suggested in a previous preliminary study. The aim of the current study was to confirm and strengthen those findings about serological IgG responses in relation to C. trachomatis serogroups and serovars.

Research paper thumbnail of A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections

European journal of gastroenterology & hepatology, 2005

This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in w... more This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfor...

Research paper thumbnail of Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection

PLoS ONE, 2012

Background: Regulation of immune responses is critical for controlling inflammation and disruptio... more Background: Regulation of immune responses is critical for controlling inflammation and disruption of this process can lead to tissue damage. We reported that CXCL13 was induced in fallopian tube tissue following C. trachomatis infection. Here, we examined the influence of the CXCL13-CXCR5 axis in chlamydial genital infection.

Research paper thumbnail of The true ligand of the NOD2 receptor is peptidoglycan instead of lipopolysaccharide: A schematic representation of ligand-receptor interactions and NF-κB activation

Gastroenterology, 2004

Reply. I thank Danese et al. for their comments about our editorial on the induction of matrix me... more Reply. I thank Danese et al. for their comments about our editorial on the induction of matrix metalloproteinase-9 (MMP-9) expression by Helicobacter pylori infection. 1 They report in their letter that MMP-9 expression has been reduced after H. pylori eradication both in epithelial cells and in mucosal fibroblasts. I acknowledge that their data confirm my findings and support my conclusions. I read with interest the data from this eradication study. They report no change of MMP-9 expression after eradication in macrophages. I observed no association between MMP-9 expression and H. pylori infection in macrophages in gastric ulcers. 1 These results suggest distinct mechanism of MMP-9 expression between epithelial cells and fibroblasts, and macrophages. MMP-9 expression in epithelial cells and fibroblasts is dependent on H. pylori infection, whereas in macrophages it is independent of H. pylori infection. The increase of MMP-9 in macrophages may be causally linked to the mucosal injury. The plasma levels of MMP-9 in patients with gastric cancer were significantly higher than those in healthy individuals. 2 It is possible that the plasma levels of MMP-9 are increased in patients with H. pyloriassociated gastritis and gastric ulcer. I am under investigation the plasma levels of MMP-9 in these patients.

Research paper thumbnail of The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology

The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the t... more The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women.

Research paper thumbnail of Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

Background: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal t... more Background: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components.

Research paper thumbnail of TRAIL-R1 is a negative regulator of pro-inflammatory responses and modulates long-term sequelae resulting from Chlamydia trachomatis infections in humans

PloS one, 2014

The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncon... more The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncontrolled inflammation can enhance pathology. In mice, TNF-related apoptosis-inducing ligand receptor (TRAIL-R), known for its effects on apoptosis, also regulates inflammation. In humans, the four homologues of TRAIL-R had never been investigated for effects on inflammation. Here, we examined whether TRAIL-R regulates inflammation during chlamydial infection. We examined TRAIL-R1 single nucleotide polymorphisms (SNPs) in an Ecuadorian cohort with and without C. trachomatis infections. There was a highly significant association for the TRAIL+626 homozygous mutant GG for infection vs no infection in this population. To confirm the results observed in the human population, primary lung fibroblasts and bone marrow-derived macrophages (BMDMs) were isolated from wildtype (WT) and TRAIL-R-deficient mice, and TRAIL-R1 levels in human cervical epithelial cells were depleted by RNA interference. In...