Faculty Opinions recommendation of Chlamydia trachomatis-infected host cells resist dsRNA-induced apoptosis.

The obligate intracellular bacterium Chlamydia trachomatis activates the host cell apoptosis pathway at a late stage of its developmental cycle. However, whether caspase-3, which is a key enzyme of apoptosis, is activated in Chlamydia-infected cells remains unknown. Here, we established HEp-2 cells stably expressing cFluc-DEVD, which is a caspase-3 substrate sequence inserted into cyclic firefly luciferase, and then monitored the dynamics of caspase-3 activity in cells infected with Chlamydia. Transfected cells without infection showed a significant increase in luciferase activity due to stimulation with staurosporine, an inducer of apoptosis. Activation was significantly blocked by addition of caspase inhibitor z-VAD-fmk. Furthermore, as expected, Chlamydia infection caused a significant increase in luciferase activation at 36–48 h postinfection with a contrastive decrease at 24 h postinfection, which is already well known. Such activation caused by the infection was much stronger when the amount of bacteria was increased. Thus, caspase-3 activation was accurately monitored by the luciferase activity in HEp-2 cells constitutively expressing the cFluc-DEVD probe. Furthermore, our data showed that C. trachomatis activates caspase-3 in host cells at a late stage of infection.

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Faculty Opinions recommendation of Chlamydia trachomatis enters a viable but non-cultivable (persistent) state within herpes simplex virus type 2 (HSV-2) co-infected host cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1030861.360564 ◽

2006 ◽

Author(s):

Rino Rappuoli

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Chlamydia Trachomatis ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Host Cells ◽

Infected Host ◽

Simplex Virus

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Chlamydia trachomatis enters a viable but non-cultivable (persistent) state within herpes simplex virus type 2 (HSV-2) co-infected host cells

Cellular Microbiology ◽

10.1111/j.1462-5822.2005.00608.x ◽

2006 ◽

Vol 8 (1) ◽

pp. 149-162 ◽

Cited By ~ 44

Author(s):

Srilekha Deka ◽

Jennifer Vanover ◽

Sophie Dessus-Babus ◽

Judy Whittimore ◽

Mary K. Howett ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Chlamydia Trachomatis ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Host Cells ◽

Infected Host ◽

Simplex Virus

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Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

BMC Genomics ◽

10.1186/1471-2164-10-252 ◽

2009 ◽

Vol 10 (1) ◽

pp. 252 ◽

Cited By ~ 31

Author(s):

Jaime A Costales ◽

Johanna P Daily ◽

Barbara A Burleigh

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Trypanosoma Cruzi ◽

Host Cells ◽

Infected Host ◽

Mrna Profiling ◽

Independent Gene ◽

Cell Cycle Block

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Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced by Vibrio cholerae

Toxins ◽

10.3390/toxins13010012 ◽

2020 ◽

Vol 13 (1) ◽

pp. 12

Author(s):

Kohei Ogura ◽

Kinnosuke Yahiro ◽

Joel Moss

Keyword(s):

Cell Death ◽

Protein Kinase ◽

Vibrio Cholerae ◽

Elongation Factor ◽

Host Cells ◽

Mitogen Activated Protein Kinase ◽

Pseudomonas Exotoxin A ◽

Tnf Α ◽

Induced Apoptosis ◽

Adp Ribosyltransferase

Pathogenic microorganisms produce various virulence factors, e.g., enzymes, cytotoxins, effectors, which trigger development of pathologies in infectious diseases. Cholera toxin (CT) produced by O1 and O139 serotypes of Vibrio cholerae (V. cholerae) is a major cytotoxin causing severe diarrhea. Cholix cytotoxin (Cholix) was identified as a novel eukaryotic elongation factor 2 (eEF2) adenosine-diphosphate (ADP)-ribosyltransferase produced mainly in non-O1/non-O139 V. cholerae. The function and role of Cholix in infectious disease caused by V. cholerae remain unknown. The crystal structure of Cholix is similar to Pseudomonas exotoxin A (PEA) which is composed of an N-terminal receptor-recognition domain and a C-terminal ADP-ribosyltransferase domain. The endocytosed Cholix catalyzes ADP-ribosylation of eEF2 in host cells and inhibits protein synthesis, resulting in cell death. In a mouse model, Cholix caused lethality with severe liver damage. In this review, we describe the mechanism underlying Cholix-induced cytotoxicity. Cholix-induced apoptosis was regulated by mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways, which dramatically enhanced tumor necrosis factor-α (TNF-α) production in human liver, as well as the amount of epithelial-like HepG2 cancer cells. In contrast, Cholix induced apoptosis in hepatocytes through a mitochondrial-dependent pathway, which was not stimulated by TNF-α. These findings suggest that sensitivity to Cholix depends on the target cell. A substantial amount of information on PEA is provided in order to compare/contrast this well-characterized mono-ADP-ribosyltransferase (mART) with Cholix.

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Differential Regulation of Inflammatory Cytokine Secretion by Human Dendritic Cells upon Chlamydia trachomatis Infection

Infection and Immunity ◽

10.1128/iai.72.12.7231-7239.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7231-7239 ◽

Cited By ~ 57

Author(s):

Ana Gervassi ◽

Mark R. Alderson ◽

Robert Suchland ◽

Jean François Maisonneuve ◽

Kenneth H. Grabstein ◽

...

Keyword(s):

Dendritic Cells ◽

Chlamydia Trachomatis ◽

Wide Spectrum ◽

Cytokine Secretion ◽

Host Cells ◽

Microbial Pathogens ◽

Potential Contribution ◽

Necrosis Factor Alpha ◽

Chlamydia Trachomatis Infection ◽

Tnf Α

ABSTRACT Chlamydia trachomatis is an obligate intracellular gram-negative bacterium responsible for a wide spectrum of diseases in humans. Both genital and ocular C. trachomatis infections are associated with tissue inflammation and pathology. Dendritic cells (DC) play an important role in both innate and adaptive immune responses to microbial pathogens and are a source of inflammatory cytokines. To determine the potential contribution of DC to the inflammatory process, human DC were infected with C. trachomatis serovar E or L2. Both C. trachomatis serovars were found to infect and replicate in DC. Upon infection, DC up-regulated the expression of costimulatory (B7-1) and cell adhesion (ICAM-1) molecules. Furthermore, chlamydial infection induced the secretion of interleukin-1β (IL-1β), IL-6, IL-8, IL-12p70, IL-18, and tumor necrosis factor alpha (TNF-α). The mechanisms involved in Chlamydia-induced IL-1β and IL-18 secretion differed from those of the other cytokines. Chlamydia-induced IL-1β and IL-18 secretion required infection with viable bacteria and was associated with the Chlamydia-induced activation of caspase-1 in infected host cells. In contrast, TNF-α and IL-6 secretion did not require that the Chlamydia be viable, suggesting that there are at least two mechanisms involved in the Chlamydia-induced cytokine secretion in DC. Interestingly, an antibody to Toll-like receptor 4 inhibited Chlamydia-induced IL-1β, IL-6, and TNF-α secretion. The data herein demonstrate that DC can be infected by human C. trachomatis serovars and that chlamydial components regulate the secretion of various cytokines in DC. Collectively, these data suggest that DC play a role in the inflammatory processes caused by chlamydial infections.

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Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression

International Journal of Molecular Sciences ◽

10.3390/ijms19103187 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3187 ◽

Cited By ~ 8

Author(s):

Eun Lim ◽

Yu Yoon ◽

Jeonghoon Heo ◽

Tae Lee ◽

Young-Ho Kim

Keyword(s):

Lung Cancer ◽

Protein Stability ◽

Cancer Cells ◽

Death Receptor ◽

Proteolytic Processing ◽

Receptor Expression ◽

Host Cells ◽

Lung Cancer Cells ◽

Regulation Of Transcription ◽

Induced Apoptosis

Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.

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