TRAIL Induces Neutrophil Apoptosis and Dampens Sepsis-Induced Organ Injury in Murine Colon Ascendens Stent Peritonitis

Beyer, Katharina; Poetschke, Christian; Partecke, Lars Ivo; Bernstorff, Wolfram von; Maier, Stefan A.; Broeker, B. M.; Heidecke, Claus–Dieter

doi:10.1371/journal.pone.0097451

Cited by 21 publications

(25 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 16 Furthermore, we have detected increased fractions of apoptotic neutrophils, resulting in a decreased number of neutrophils within the septic organs and less tissue damage in TRAIL-treated animals during sepsis. 17 These results are supported by findings in other models of sepsis. 18 However, there are also reports indicating that TRAIL is involved in immune unresponsiveness following sepsis.…”

Section: Introductionsupporting

confidence: 75%

TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis

Beyer

Stollhof

Poetschke

et al. 2016

JIR

Self Cite

View full text Add to dashboard Cite

BackgroundApart from inducing apoptosis in tumor cells, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) influences inflammatory reactions. Murine colon ascendens stent peritonitis (CASP) represents a model of diffuse peritonitis. Recently, it has been demonstrated that administration of exogenous TRAIL not only induces apoptosis in neutrophils but also enhances survival in this model. The aim of this study was to examine the impact of genetic TRAIL deficiency on the course of CASP.MethodsPeritonitis was induced in 6- to 8-week-old female TRAIL−/− mice as well as in wild-type mice. The sepsis severity score and survival of mice were monitored. Bacterial loads in blood as well as in the lymphoid organs were examined. Additionally, the number of apoptotic cells within the lymphoid organs was determined.ResultsAs early as 8 hours postinduction of CASP, TRAIL−/− mice were significantly more affected by sepsis than wild-type mice, as measured by the sepsis severity score. However, during the further course of sepsis, TRAIL deficiency led to significantly decreased sepsis severity scores, resulting in an enhanced overall survival in TRAIL−/− mice. The better survival of TRAIL−/− mice was accompanied by a decreased bacterial load within the blood. In marked contrast, the number of apoptotic cells within the lymphoid organs was highly increased in TRAIL−/− mice 20 hours after induction of CASP.ConclusionHence, exogenous and endogenous TRAIL is protective during the early phase of sepsis, while endogenous TRAIL appears to be detrimental in the later course of this disease.

show abstract

Section: Introductionsupporting

confidence: 75%

TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis

Beyer

Stollhof

Poetschke

et al. 2016

JIR

Self Cite

View full text Add to dashboard Cite

show abstract

“…At sites of inflammation, TRAIL has also been shown to induce apoptosis of neutrophils, which are then phagocytized by macrophages favoring the resolution of inflammation [53,54] . Remarkably, in the lungs of IL37tg mice, we observed significant lower levels of TRAIL mRNA at 48 h after infection, despite increased alveolar recruitment of AMs and neutrophils, demonstrating that the initiation of the resolution phase of infection is affected by IL-37 expression.…”

Section: Discussionmentioning

confidence: 99%

“…We further observed marked death and decay of neutrophils in the lungs of infected IL-37tg mice. Neutrophils were most likely recruited by the increased expression of chemokines and subsequently failed to undergo controlled cell death because of reduced TRAIL expression [54] . This cascade likely contributed to increased tissue damage and pneumococcal spread as well as the development of necrotizing pneumonia and increased mortality [5,55] .…”

Section: Discussionmentioning

confidence: 99%

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

et al. 2017

View full text Add to dashboard Cite

Streptococcus pneumoniae infections can lead to severe complications with excessive immune activation and tissue damage. Interleukin-37 (IL-37) has gained importance as a suppressor of innate and acquired immunity, and its effects have been therapeutic as they prevent tissue damage in autoimmune and inflammatory diseases. By using RAW macrophages, stably transfected with human IL-37, we showed a 70% decrease in the cytokine levels of IL-6, TNF-α, and IL-1β, and a 2.2-fold reduction of the intracellular killing capacity of internalized pneumococci in response to pneumococcal infection. In a murine model of infection with S. pneumoniae, using mice transgenic for human IL-37b (IL-37tg), we observed an initial decrease in cytokine expression of IL-6, TNF-α, and IL-1β in the lungs, followed by a late-phase enhancement of pneumococcal burden and subsequent increase of proinflammatory cytokine levels. Additionally, a marked increase in recruitment of alveolar macrophages and neutrophils was noted, while TRAIL mRNA was reduced 3-fold in lungs of IL-37tg mice, resulting in necrotizing pneumonia with augmented death of infiltrating neutrophils, enhanced bacteremic spread, and increased mortality. In conclusion, we have identified that IL-37 modulates several core components of a successful inflammatory response to pneumococcal pneumonia, which lead to increased inflammation, tissue damage, and mortality.

show abstract

“…However, more recently it has been discovered that TRAIL also exerts a negative impact on immune cells [27, 29, 30] demonstrating promotion of tumour growth in a murine model of pancreatic cancer [31]. …”

Section: Discussionmentioning

confidence: 99%

LPS promotes resistance to TRAIL-induced apoptosis in pancreatic cancer

Beyer

Partecke

Roetz

et al. 2017

Infect Agents Cancer

Self Cite

View full text Add to dashboard Cite

BackgroundThough TRAIL has been hailed as a promising drug for tumour treatment, it has been observed that many tumour cells have developed escape mechanisms against TRAIL-induced apoptosis. As a receptor of LPS, TLR 4, which is expressed on a variety of cancer cells, can be associated with TRAIL-resistance of tumour cells and tumour progression as well as with the generation of an anti-tumour immune response.MethodsIn this study, the sensitivity to TRAIL-induced apoptosis as well as the influence of LPS-co-stimulation on the cell viability of the pancreatic cancer cell lines PANC-1, BxPC-3 and COLO 357 was examined by FACS analyses and a cell viability assay. Subsequently, the expression of TRAIL-receptors was detected via FACS analyses. Levels of osteoprotegerin (OPG) were also determined using an enzyme-linked immunosorbent assay.ResultsPANC-1 cells were shown to be resistant to TRAIL-induced apoptosis. This was accompanied by significantly increased osteoprotegerin levels and a significantly decreased expression of DR4.In contrast, TRAIL significantly induced apoptosis in COLO 357 cells and to a lesser degree in BxPC-3 cells. Co-stimulation of COLO 357 as well as BxPC-3 cells combining TRAIL and LPS resulted in a significant decrease in TRAIL-induced apoptosis. In COLO 357 cells TRAIL-stimulation decreased the levels of OPG thereby not altering the expression of the TRAIL-receptors 1–4 resulting in a high susceptibility to TRAIL-induced apoptosis. Co-stimulation with LPS and TRAIL completely reversed the effect of TRAIL on OPG levels reaching a 2-fold increase beyond the level of non-stimulated cells resulting in a lower susceptibility to apoptosis.In BxPC-3, TRAIL stimulation decreased the expression of DR4 and significantly increased the decoy receptors TRAIL-R3 and TRAIL-R4 leading to a decrease in TRAIL-induced apoptosis. OPG levels remained unchanged. Co-stimulation with TRAIL and LPS further enhanced the changes in TRAIL-receptor-expression promoting apoptosis resistance.ConclusionsHere it has been shown that TRAIL-resistance in pancreatic cancer cells can be mediated by the inflammatory molecule LPS as well as by different expression patterns of functional and non-functional TRAIL-receptors.

show abstract

TRAIL Induces Neutrophil Apoptosis and Dampens Sepsis-Induced Organ Injury in Murine Colon Ascendens Stent Peritonitis

Cited by 21 publications

References 29 publications

TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis

TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

LPS promotes resistance to TRAIL-induced apoptosis in pancreatic cancer

Contact Info

Product

Resources

About