In VitroEffects ofClostridium DifficileToxins on Hepatocytes

Mazuski, John E.; Panesar, Ninder; Tolman, Kim; Longo, Walter E.

doi:10.1006/jsre.1998.5398

Cited by 8 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…C. difficile disease is thought to be secondary to the release of toxins A and B from pathogenic strains of the bacterium. In previous studies of the hepatocyte acute-phase response we found that C. difficile toxins stimulated acute-phase protein production by hepatocytes [26,27], and IL-1 RA inhibited the C. difficile-induced acute-phase protein production [27]. This was in striking contrast to LPStriggered induction of acute-phase proteins, which was not influenced by IL-1 RA.…”

Section: Discussioncontrasting

confidence: 60%

“…Since IL-1 RA has been shown to decrease C. difficile toxin-stimulated acute-phase protein production by hepatocytes [26], we examined the effect of high-dose IL-1 RA (100 g/ml) on toxin-mediated actin rearrangement. Unlike acute-phase protein synthesis, the addition of IL-1 RA to the culture medium had no effect on C. difficile toxin-induced cytoskeletal collapse (Fig.…”

Section: Confocal Microscopy Of the Actin Cytoskeletonmentioning

confidence: 99%

“…difficile infections are accompanied by a vigorous systemic inflammatory response. In previous studies, we observed that C. difficile toxin A and toxin B could directly stimulate synthesis of a 23-kDa murine acutephase protein, and that this effect was blocked by the addition of interleukin-1 receptor antagonist (IL-1 RA) [26,27]. IL-1 RA binds with high affinity to the IL-1 receptor without initiating signal transduction [28,29].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clostridium difficile Toxin: Cytoskeletal Changes and Lactate Dehydrogenase Release in Hepatocytes

Grossmann¹,

Longo²,

Kaminski³

et al. 2000

Journal of Surgical Research

Self Cite

View full text Add to dashboard Cite

Section: Discussioncontrasting

confidence: 60%

Section: Confocal Microscopy Of the Actin Cytoskeletonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clostridium difficile Toxin: Cytoskeletal Changes and Lactate Dehydrogenase Release in Hepatocytes

Grossmann¹,

Longo²,

Kaminski³

et al. 2000

Journal of Surgical Research

Self Cite

View full text Add to dashboard Cite

“…8,12,14,16 C. difficile produces two toxins (toxins A and B) in its vegetative form, both of which are cytotoxic to human intestine epithelial cells. Both toxins have been shown to stimulate hepatocyte acute phase protein synthesis in vitro 17 and TNF-␣ has been shown to mediate the cytotoxicity of toxin A. 18 It is possible that C. difficile toxins aggravate GVHD by increasing the release of TNF-␣ and related proteins and thus promoting the cytokine dysregulation induced by high-dose chemo-radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality

Chakrabarti

Lees

et al. 2000

Bone Marrow Transplant

121

118

View full text Add to dashboard Cite

Summary:We retrospectively evaluated 75 allogeneic stem cell transplant recipients to ascertain the incidence, risk factors and outcome of infection with Clostridium difficile. Ten patients (13%) had Clostridium difficile infection at a median of 38 days (range day −6 to day +72) following the transplant. There was no difference in the duration or severity of diarrhoea in patients with Clostridium difficile infection compared to the uninfected patients and no relationship to the prior antibiotic or chemotherapy usage, age, gender, underlying disease, donor type, CMV serostatus, total body irradiation or time to engraftment. The incidence of viral infections was increased in patients infected with Clostridium difficile (7/10 vs 15/65, P = 0.005, odds ratio 7.7), but the strongest association was with GVHD Ͼgrade 2 (5/10 vs 6/65 uninfected patients, P = 0.004, odds ratio 9.8). Patients infected with Clostridium difficile also suffered a higher non-relapse mortality with 7/10 patients succumbing to either GVHD or infections, compared to 19/65 patients in the uninfected group (P = 0.02, odds ratio 5.6). Thus Clostridium difficile infections in our study had a strong association with GVHD and increased non-relapse mortality. It is possible that Clostridium difficile toxin might predispose to increased severity of GVHD leading to an adverse outcome. Bone Marrow Transplantation (2000) 26, 871-876.

show abstract

“…As a result, cultured cells treated with TcdB exhibit changes in cell morphology and undergo apoptosis, eventually leading to the death of the cell (8)(9)(10). TcdB intoxicates numerous cell types in vitro, including fibroblasts, neuronal cells, epithelial cells, endothelial cells, lymphocytes, and hepatocytes (4,(11)(12)(13)(14)(15), yet whether any of these cell types are targeted during C. difficile-associated disease (CDAD) is unknown.…”

mentioning

confidence: 99%

Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish embryo model of intoxication

Hamm

Voth

Ballard

2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Clostridium difficile toxin B (TcdB) has been studied extensively by using cell-free systems and tissue culture, but, like many bacterial toxins, the in vivo targets of TcdB are unknown and have been difficult to elucidate with traditional animal models. In the current study, the transparent Danio rerio (zebrafish) embryo was used as a model for imaging of in vivo TcdB localization and organ-specific damage in real time. At 24 h after treatment, TcdB was found to localize at the pericardial region, and zebrafish exhibited the first signs of cardiovascular damage, including a 90% reduction in systemic blood flow and a 20% reduction in heart rate. Within 72 h of exposure to TcdB, the ventricle chamber of the heart became deformed and was unable to contract or pump blood, and the fish exhibited extensive pericardial edema. In line with the observed defects in ventricle contraction, TcdB was found to directly disrupt coordinated contractility and rhythmicity in primary cardiomyocytes. Furthermore, using a caspase-3 inhibitor, we were able to block TcdB-related cardiovascular damage and prevent zebrafish death. These findings present an insight into the in vivo targets of TcdB, as well as demonstrate the strength of the zebrafish embryo as a tractable model for identification of in vivo targets of bacterial toxins and evaluation of novel candidate therapeutics.bacterial toxin ͉ Clostridium difficile-associated disease ͉ large clostridial toxins

show abstract

In VitroEffects ofClostridium DifficileToxins on Hepatocytes

Cited by 8 publications

References 31 publications

Clostridium difficile Toxin: Cytoskeletal Changes and Lactate Dehydrogenase Release in Hepatocytes

Clostridium difficile Toxin: Cytoskeletal Changes and Lactate Dehydrogenase Release in Hepatocytes

Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality

Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish embryo model of intoxication

Contact Info

Product

Resources

About