TY  - JOUR
A1  - Pachel, Christina
A1  - Mathes, Denise
A1  - Bayer, Barbara
A1  - Dienesch, Charlotte
A1  - Wangorsch, Gaby
A1  - Heitzmann, Wolfram
A1  - Lang, Isabell
A1  - Ardehali, Hossein
A1  - Ertl, Georg
A1  - Dandekar, Thomas
A1  - Wajant, Harald
A1  - Frantz, Stefan
T1  - Exogenous Administration of a Recombinant Variant of TWEAK Impairs Healing after Myocardial Infarction by Aggravation of Inflammation
JF  - PLoS ONE
N2  - Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factorinducible 14 (Fn14) are upregulated after myocardial infarction (MI) in both humans and mice. They modulate inflammation and the extracellular matrix, and could therefore be important for healing and remodeling after MI. However, the function of TWEAK after MI remains poorly defined.
Methods and results: Following ligation of the left coronary artery, mice were injected twice per week with a recombinant human serum albumin conjugated variant of TWEAK (HSA-Flag-TWEAK), mimicking the activity of soluble TWEAK. Treatment with HSA-Flag-TWEAK resulted in significantly increased mortality in comparison to the placebo group due to myocardial rupture. Infarct size, extracellular matrix remodeling, and apoptosis rates were not different after MI. However, HSA-Flag-TWEAK treatment increased infiltration of proinflammatory cells into the myocardium. Accordingly, depletion of neutrophils prevented cardiac ruptures without modulating all-cause mortality.
Conclusion: Treatment of mice with HSA-Flag-TWEAK induces myocardial healing defects after experimental MI. This is mediated by an exaggerated neutrophil infiltration into the myocardium.
KW  - apoptosis
KW  - myocardial infarction
KW  - neutrophils
KW  - cytokines
KW  - inflammation
KW  - myocardium
KW  - heart
KW  - extracellular matrix
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129889
VL  - 8
IS  - 11
ER  - 
TY  - JOUR
A1  - Chopra, Martin
A1  - Lang, Isabell
A1  - Salzmann, Steffen
A1  - Pachel, Christina
A1  - Kraus, Sabrina
A1  - Bäuerlein, Carina A.
A1  - Brede, Christian
A1  - Jordán Garrote, Ana-Laura
A1  - Mattenheimer, Katharina
A1  - Ritz, Miriam
A1  - Schwinn, Stefanie
A1  - Graf, Carolin
A1  - Schäfer, Viktoria
A1  - Frantz, Stefan
A1  - Einsele, Hermann
A1  - Wajant, Harald
A1  - Beilhack, Andreas
T1  - Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1
JF  - PLoS ONE
N2  - Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5%), TNF deficient (12.5%), and TNFR2 deficient mice (22.2%) were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4+ T cells and CD4+ forkhead box P3 (FoxP3)+ regulatory T cells (Treg) but reduced numbers of CD8+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome.
KW  - Bioluminescence
KW  - cancer treatment
KW  - cell staining
KW  - cytokines
KW  - immune cells
KW  - metastasis
KW  - regulatory T cells
KW  - T cells
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97246
ER  -