scholarly journals The TWEAK/Fn14/CD163 axis—implications for metabolic disease

2021 ◽  
Author(s):  
Wiktoria Ratajczak ◽  
Sarah D Atkinson ◽  
Catriona Kelly
Keyword(s):  
Metabolic Disease ◽  
Tumor Necrosis ◽  
Tissue Type ◽  
Soluble Form ◽  
Signalling Pathways ◽  
Cellular Events ◽  
Intracellular Signalling Pathways ◽  
Tnf Superfamily ◽  
Membrane Bound ◽  
Necrosis Factor

AbstractTWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK – Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression.

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.

Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2284-2289 ◽  
Author(s):  
VW van Hinsbergh ◽  
KA Bauer ◽  
T Kooistra ◽  
C Kluft ◽  
G Dooijewaard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Plasminogen Activator ◽  
Tumor Necrosis ◽  
Degradation Products ◽  
Tissue Type ◽  
Necrosis Factor ◽  
Pai 1

Abstract Several investigators have reported that tumor necrosis factor (TNF) can alter the production of plasminogen activator type-1 (PAI-1) and plasminogen activators (PAs) by endothelial cells in vitro. We have examined the in vivo effects of recombinant human TNF administration on fibrinolysis as assessed by parameters in plasma during a 24-hour period of continuous TNF infusion to 17 cancer patients with active disease. The plasma levels of PAI activity increased sevenfold after 3 and 24 hours of TNF infusion. This was the result of an increase of PAI- 1 antigen; PAI-2 antigen was not detectable. Plasma concentrations of tissue-type PA (t-PA) antigen increased twofold to fivefold after 3 and 24 hours of TNF infusion, whereas urokinase-type PA antigen levels in plasma remained unaltered. After 3 hours of TNF infusion the plasma levels of alpha 2-antiplasmin were slightly decreased, 5% on average, suggesting that fibrinolysis continued. After 24 hours of TNF infusion a highly significant increase in fibrin- plus fibrinogen-degradation products, and separately of fibrin degradation products and fibrinogen degradation products, was found. This indicates that fibrinolysis persisted, at least partly, in the presence of high levels of PAI activity. Whereas PAI-1 production increased, t-PA production by human endothelial cells in vitro remains unaltered or even decreases on TNF addition. It has been shown previously that TNF infusion in our patients results in thrombin and fibrin generation. Therefore, it is possible that thrombin, not TNF, is the actual stimulus for t-PA production in our patients. We speculate that fibrin is formed during TNF infusions and that plasmin is generated by t-PA action immediately on the initial formation of (soluble) fibrin molecules. Such a process may explain the generation of degradation products of both fibrin and fibrinogen during infusion of TNF in patients.

scholarly journals Baff Binds to the Tumor Necrosis Factor Receptor–Like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population

2000 ◽  
Vol 192 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Jeffrey S. Thompson ◽  
Pascal Schneider ◽  
Susan L. Kalled ◽  
LiChun Wang ◽  
Eric A. Lefevre ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Cell Population ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

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