scholarly journals Neutralization of Tumor Necrosis Factor (TNF) by Antibody but not TNF Receptor Fusion Molecule Exacerbates Chronic Murine Tuberculosis

2007 ◽  
Vol 195 (11) ◽  
pp. 1643-1650 ◽  
Author(s):  
Hillarie L. Plessner ◽  
P. Ling Lin ◽  
Tadahiko Kohno ◽  
James S. Louie ◽  
Denise Kirschner ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Necrosis Factor

scholarly journals The α and β Subunits of IκB Kinase (IKK) Mediate TRAF2-Dependent IKK Recruitment to Tumor Necrosis Factor (TNF) Receptor 1 in Response to TNF

2001 ◽  
Vol 21 (12) ◽  
pp. 3986-3994 ◽  
Author(s):  
Anne Devin ◽  
Yong Lin ◽  
Shoji Yamaoka ◽  
Zhiwei Li ◽  
Michael Karin ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leucine Zipper ◽  
Nuclear Translocation ◽  
Ring Finger ◽  
Tnf Receptor ◽  
Death Domain ◽  
Iκb Kinase ◽  
Cytokine Tumor Necrosis Factor ◽  
Necrosis Factor

ABSTRACT The activation of IκB kinase (IKK) is a key step in the nuclear translocation of the transcription factor NF-κB. IKK is a complex composed of three subunits: IKKα, IKKβ, and IKKγ (also called NEMO). In response to the proinflammatory cytokine tumor necrosis factor (TNF), IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor-associated factor 2 (TRAF2). We found that the IKKα and IKKβ catalytic subunits are required for IKK-TRAF2 interaction. This interaction occurs through the leucine zipper motif common to IKKα, IKKβ, and the RING finger domain of TRAF2, and either IKKα or IKKβ alone is sufficient for the recruitment of IKK to TNF-R1. Importantly, IKKγ is not essential for TNF-induced IKK recruitment to TNF-R1, as this occurs efficiently in IKKγ-deficient cells. Using TRAF2−/− cells, we demonstrated that the TNF-induced interaction between IKKγ and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2.

scholarly journals Membrane lymphotoxin-α2β is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Kirstin Kucka ◽  
Isabell Lang ◽  
Tengyu Zhang ◽  
Daniela Siegmund ◽  
Juliane Medler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Asymmetric Structure ◽  
Tnf Receptor ◽  
Membrane Bound ◽  
Necrosis Factor

AbstractIn the early 1990s, it has been described that LTα and LTβ form LTα2β and LTαβ2 heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ2–LTβR system has been intensively studied while the LTα2β–TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα2β–TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα2β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα2β (memLTα2β), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα2β is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.

Tumor necrosis factor-α inhibitors alleviation of experimentally induced neuropathic pain is associated with modulation of TNF receptor expression

2014 ◽  
Vol 92 (11) ◽  
pp. 1490-1498 ◽  
Author(s):  
Pablo Andrade ◽  
Govert Hoogland ◽  
John S. Del Rosario ◽  
Harry W. Steinbusch ◽  
Veerle Visser-Vandewalle ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Receptor Expression ◽  
Tnf Receptor ◽  
Factor Α ◽  
Necrosis Factor ◽  
Experimentally Induced

scholarly journals Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor.

1993 ◽  
Vol 268 (25) ◽  
pp. 18542-18548
Author(s):  
L.A. Tartaglia ◽  
D. Pennica ◽  
D.V. Goeddel
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Necrosis Factor

Tumor Necrosis Factor (TNF) α quantification by ELISA and bioassay: effects of TNFα-soluble TNF receptor (p55) complex dissociation during assay incubations

1994 ◽  
Vol 177 (1-2) ◽  
pp. 191-198 ◽  
Author(s):  
Angelo Corti ◽  
Claudio Poiesi ◽  
Silvia Merli ◽  
Giovanni Cassani
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Tnf Α ◽  
Soluble Tnf Receptor ◽  
Necrosis Factor

scholarly journals Retinoids downregulate both p60 and p80 forms of tumor necrosis factor receptors in human histiocytic lymphoma U-937 cells

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3547-3555 ◽  
Author(s):  
K Totpal ◽  
MM Chaturvedi ◽  
R LaPushin ◽  
BB Aggarwal
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leukemia Cell Line ◽  
Cell Surface Expression ◽  
Scatchard Analysis ◽  
Dependent Manner ◽  
Tnf Receptor ◽  
Tnf Receptors ◽  
Histiocytic Lymphoma ◽  
Necrosis Factor

Because retinoids are known to modulate the growth and differentiation effects of tumor necrosis factor (TNF), we investigated the effect of all-trans-retinoic acid (RA) on the cell surface expression of TNF receptors in human histiocytic lymphoma U-937 cells. RA decreased the specific binding of 125I-labeled TNF to these cells in a dose- and time-dependent manner. The maximal decrease occurred when cells were treated with 1 mumol/L RA for 24 hours at 37 degrees C. Scatchard analysis of the binding indicated that the decrease by RA was caused by a decrease in receptor number and not by a decrease in affinity. The downmodulation of TNF receptors was also confirmed by covalent receptor-ligand cross-linking studies. Receptor-mediated internalization of the ligand was also found to be decreased on treatment of cells with RA. Northern blot analysis also indicated a decrease in the transcript of the receptor. By using antibodies specific to either the p60 or p80 form of the TNF receptor, we found that both receptors were downregulated by RA. RA treatment also decreased TNF receptors on acute monocytic leukemia cell line THP-1. Other analogues of RA, specifically 9-cis-RA, (E)-4-[2-(5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl]-benzoic acid (TTNPB), and 3-methyl-TTNPB, which differ in their specificity towards different RA receptors, were also active in downregulating TNF receptors. 3-Methyl-TTNPB, which is more specific for the RXR form of the RA receptor, was found to be most potent. The downregulation of TNF receptors by RA correlated with the downmodulation of the antiproliferative effects of TNF against U-937 cells. Overall, our results indicate that RA downmodulates both the p60 and p80 form of the TNF receptor on cells of myeloid origin, which correlates with the cellular response.

scholarly journals Inhibition of Tumor Necrosis Factor (TNF) Signal Transduction by the Adenovirus Group C RID Complex Involves Downregulation of Surface Levels of TNF Receptor 1

2004 ◽  
Vol 78 (23) ◽  
pp. 13113-13121 ◽  
Author(s):  
Shawn P. Fessler ◽  
Y. Rebecca Chin ◽  
Marshall S. Horwitz
Keyword(s):  
Plasma Membrane ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Signaling Complex ◽  
Antiviral Responses ◽  
Mechanism Of Inhibition ◽  
Early Transcription ◽  
Necrosis Factor ◽  
Inhibit Tumor Necrosis Factor

ABSTRACT Adenoviruses employ multiple genes to inhibit the host antiviral responses. There is increasing evidence that these immunoregulatory genes may function either during lytic or latent infection. Adenovirus early transcription region 3 (E3) encodes at least seven proteins, five of which block the acquired or innate immune response. Previous findings from this laboratory demonstrated that the E3 proteins 10.4K and 14.5K, which form a complex in the plasma membrane, inhibit tumor necrosis factor (TNF)-induced activation of NF-κB and the synthesis of chemokines. To determine the mechanism of inhibition of these pathways by the adenovirus E3 10.4K/14.5K proteins, we have examined the effects of this viral complex on the inhibition of AP-1 and NF-κB activation by TNF and found a reduction in assembly of the TNF receptor 1 (TNFR1) signaling complex at the plasma membrane accompanied by downregulation of surface levels of TNFR1.

scholarly journals Downregulation of tumor necrosis factor (TNF) sensitivity via modulation of TNF binding capacity by protein kinase C activators.

1987 ◽  
Vol 166 (6) ◽  
pp. 1788-1797 ◽  
Author(s):  
R Unglaub ◽  
B Maxeiner ◽  
B Thoma ◽  
K Pfizenmaier ◽  
P Scheurich
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Binding Capacity ◽  
Receptor Protein ◽  
Tnf Alpha ◽  
Tnf Receptor ◽  
Kinase C ◽  
Necrosis Factor

The regulatory action of activators for protein kinase C on the specific binding capacity for recombinant human tumor necrosis factor alpha (TNF-alpha) was studied on various human cell lines. Phorbol myristate acetate (PMA) and oleyl acetyl glycerol (OAG) both are able to rapidly downregulate TNF-binding capacity of normal and malignant cells derived from various tissues. As PMA treatment did not enhance internalization of TNF-alpha-receptor complexes at 37 degrees C, and since OAG was able to downregulate TNF-binding capacity under conditions where internalization and shedding of receptor protein are prevented, we conclude that protein kinase C controls ligand affinity of the TNF-receptor protein, possibly via direct phosphorylation. Protein kinase C triggered downregulation of TNF-alpha-binding capacity concomitantly resulted in reduction of TNF-alpha sensitivity, as revealed from decreased cytotoxic action of TNF-alpha on L 929 cells and from inhibition of TNF-alpha-mediated enhancement of HLA class II antigen expression in Colo 205 cells. Restoration of TNF-binding capacity upon abrogation of protein kinase C stimulation leads to full recovery of TNF responsiveness, further supporting the close linkage of TNF-receptor expression and TNF sensitivity. These data suggest that regulation of TNF-binding capacity by protein kinase C is one of the cellular control mechanisms of TNF responsiveness.

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