scholarly journals Role of SODD in Regulation of Tumor Necrosis Factor Responses

2003 ◽  
Vol 23 (11) ◽  
pp. 4026-4033 ◽  
Author(s):  
Hidetoshi Takada ◽  
Nien-Jung Chen ◽  
Christine Mirtsos ◽  
Shinobu Suzuki ◽  
Nobutaka Suzuki ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Signaling Proteins ◽  
Ligand Stimulation ◽  
Cytotoxic Responses ◽  
Necrosis Factor

ABSTRACT Signaling from tumor necrosis factor receptor type 1 (TNFR1) can elicit potent inflammatory and cytotoxic responses that need to be properly regulated. It was suggested that the silencer of death domains (SODD) protein constitutively associates intracellularly with TNFR1 and inhibits the recruitment of cytoplasmic signaling proteins to TNFR1 to prevent spontaneous aggregation of the cytoplasmic death domains of TNFR1 molecules that are juxtaposed in the absence of ligand stimulation. In this study, we demonstrate that mice lacking SODD produce larger amounts of cytokines in response to in vivo TNF challenge. SODD-deficient macrophages and embryonic fibroblasts also show altered responses to TNF. TNF-induced activation of NF-κB is accelerated in SODD-deficient cells, but TNF-induced c-Jun N-terminal kinase activity is slightly repressed. Interestingly, the apoptotic arm of TNF signaling is not hyperresponsive in the SODD-deficient cells. Together, these results suggest that SODD is critical for the regulation of TNF signaling.

scholarly journals Apparently Normal Tumor Necrosis Factor Receptor 1 Signaling in the Absence of the Silencer of Death Domains

2003 ◽  
Vol 23 (18) ◽  
pp. 6609-6617 ◽  
Author(s):  
Robert Endres ◽  
Georg Häcker ◽  
Inge Brosch ◽  
Klaus Pfeffer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Death Receptor ◽  
High Dose ◽  
Wild Type ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT The silencer of death domains (SODD) has been proposed to prevent constitutive signaling of tumor necrosis factor receptor 1 (TNFR1) in the absence of ligand. Besides TNFR1, death receptor 3 (DR3), Hsp70/Hsc70, and Bcl-2 have been characterized as binding partners of SODD. In order to investigate the in vivo role of SODD, we generated mice congenitally deficient in expression of the sodd gene. No spontaneous inflammatory infiltrations were observed in any organ of these mice. Consistent with this finding, in the absence of SODD no alteration in the activation patterns of nuclear factor κB (NF-κB), stress kinases, or ERK1 or -2 was observed after stimulation with tumor necrosis factor (TNF). Activation of NF-κB by DR3 was also unchanged. The extents of DR3- and TNF-induced apoptosis were comparable in gene-deficient and wild-type cells. Protection of cells against heat shock as mediated by the Hsp70 system and against staurosporine-induced apoptosis was independent of SODD. Furthermore, resistance to high-dose lipopolysaccharide (LPS) injections, LPS-d-GalN injections, and infection with listeriae was similar in wild-type and gene-deficient mice. In conclusion, our data do not support the concept of a unique, nonredundant role of SODD for the functions of TNFR1, Hsp70, and DR3.

The Role of the Tumor Necrosis Factor Receptor in 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis in Mice

2005 ◽  
Vol 50 (9) ◽  
pp. 1669-1676 ◽  
Author(s):  
Minoru Nakai ◽  
Kaori Sudo ◽  
Yasuhiro Yamada ◽  
Yasushi Kojima ◽  
Tomohiro Kato ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Sulfonic Acid ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Trinitrobenzene Sulfonic Acid ◽  
Necrosis Factor

scholarly journals Opposing role of tumor necrosis factor receptor 1 signaling in T cell-mediated hepatitis and bacterial infection in mice

Hepatology ◽  
2016 ◽  
Vol 64 (2) ◽  
pp. 508-521 ◽  
Author(s):  
Raluca Wroblewski ◽  
Marietta Armaka ◽  
Vangelis Kondylis ◽  
Manolis Pasparakis ◽  
Henning Walczak ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Bacterial Infection ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

scholarly journals Posttranscriptional Downregulation of c-IAP2 by the Ubiquitin Protein Ligase c-IAP1 In Vivo

2005 ◽  
Vol 25 (8) ◽  
pp. 3348-3356 ◽  
Author(s):  
Dietrich B. Conze ◽  
Lori Albert ◽  
David A. Ferrick ◽  
David V. Goeddel ◽  
Wen-Chen Yeh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Homologous Gene ◽  
Necrosis Factor Alpha ◽  
Ubiquitin Protein Ligase ◽  
Signaling Complex ◽  
Subsequent Degradation ◽  
Necrosis Factor

ABSTRACT Inhibitor of apoptosis proteins (IAPs) c-IAP1 and c-IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c-IAP1 and c-IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c-IAP1 in a physiologic setting, c-IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c-IAP1−/− mice do, however, express markedly elevated levels of c-IAP2 protein in the absence of increased c-IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-κB, resting and cytokine-induced NF-κB activation was not impaired in c-IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism.

scholarly journals Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice

2016 ◽  
Vol Volume 11 ◽  
pp. 1705-1712 ◽  
Author(s):  
Masaki Fujita ◽  
Ouchi Hiroshi ◽  
Satoshi Ikemage ◽  
Eiji Harada ◽  
Takemasa Matsumoto ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Pulmonary Emphysema ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

IN VIVO SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR RELEASE IN OKT3-TREATED PATIENTS

1995 ◽  
Vol 59 (10) ◽  
pp. 1470-1475 ◽  
Author(s):  
André Herbelin ◽  
Lucienne Chatenoud ◽  
Pascale Roux-Lombard ◽  
Donat De Groote ◽  
Christophe Legendre ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

The Role of Tumor Necrosis Factor Receptor Type 1 in Orthodontic Tooth Movement

2007 ◽  
Vol 86 (11) ◽  
pp. 1089-1094 ◽  
Author(s):  
I. Andrade ◽  
T.A. Silva ◽  
G.A.B. Silva ◽  
A.L. Teixeira ◽  
M.M. Teixeira
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tooth Movement ◽  
Tumor Necrosis Factor Receptor ◽  
Orthodontic Tooth Movement ◽  
Receptor Type ◽  
Periodontal Tissues ◽  
Tnf Α ◽  
Necrosis Factor

Orthodontic tooth movement is dependent on osteoclast activity. Tumor necrosis factor (TNF)-α plays an important role, directly or via chemokine release, in osteoclast recruitment and activation. This study aimed to investigate whether the TNF receptor type 1 (p55) influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and p55-deficient mice (p55−/−). Levels of TNF-α and 2 chemokines (MCP-1/CCL2, RANTES/CCL5) were evaluated in periodontal tissues. A significant increase in CCL2 and TNF-α was observed in both groups after 12 hrs of mechanical loading. However, CCL5 levels remained unchanged in p55−/− mice at this time-point. The number of TRAP-positive osteoclasts in p55−/− mice was significantly lower than that in WT mice. Also, there was a significantly smaller rate of tooth movement in p55−/− mice. Analysis of our data suggests that the TNFR-1 plays a significant role in orthodontic tooth movement that might be associated with changes in CCL5 levels.

scholarly journals A Critical Role of the p75 Tumor Necrosis Factor Receptor (p75TNF-R) in Organ Inflammation Independent of  TNF, Lymphotoxin α, or the p55TNF-R

1998 ◽  
Vol 188 (7) ◽  
pp. 1343-1352 ◽  
Author(s):  
Eleni Douni ◽  
George Kollias
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Wide Range ◽  
Lymphotoxin Α ◽  
Necrosis Factor

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.

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