China
Africa
Explore chapters and articles related to this topic
Endotoxin and Cancer
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Minghuang Zhang, Kevin J. Tracey
Recently, it became clear that TNF induces cell apoptosis by activating a family of “caspase” proteases via the TNF receptor 1 (TNFR1)-mediated signal pathway (Fig. 1). Following receptor aggregation triggered by TNF binding, activated TNFR1 recruits an adaptor molecule termed TNFR1-associated death domain protein (TRADD) (121). Once TRADD binds to the TNFR1 death domain in the presence of TNF, it causes recruitment of both Fas-associating protein with death domain (FADD; MORT1) and receptor interacting protein (RIP) through the C-terminal death domain and recruitment of TNF receptor-associated factor 2 (TRAF2) through N-terminal TRAF-interacting domain (122). These two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD, initiating two different pathways responsible for apoptosis induction and apoptosis protection, respectively.
Overview of the mucosal immune system structure
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Reinhard Pabst, Per Brandtzaeg
The cellular interactions involve lymphotoxins (LTs), which are members of the tumor necrosis factor (TNF) superfamily, as well as the two TNF receptors (TNF-Rs) I and II (55 and 75 kDa). A crucial differentiating event is membrane expression of LTα1β2 on the CD3−CD4+CD45+IL-7R+ LTi cells after stimulation of the receptor activator of nuclear factor (NF) κB (RANK)–TNF receptor associated factor family 6 (TRAF6) pathway and—especially in PPs—alternative cytokine signaling through the interleukin-7 receptor (IL-7R). This event is followed by LTi cell interaction with the LTβ receptor (LTβR)−positive stromal cells, which are positive for vascular cell adhesion molecule (VCAM)-1 and are called lymphoid tissue organizer cells but display a different activation profile in the organogenesis of lymph nodes and PPs. Knockout mice deficient in LTα or LTβ virtually lack lymph nodes and have no detectable PPs. The organ development also involves several feedback loops with chemokines and adhesion molecules such as CXC chemokine ligand 13 (CXCL13)–CXCR5 and CXCR5-induced α4β1integrin–VCAM-1 interactions.
The Indispensable Soma Hypothesis in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
It was shown that neurons may interfere with germline survival. Levi-Ferber et al. [92] have shown that neuronal stress induces apoptosis in the germline. This process is mediated by the IRE-1 (inositol-requiring enzyme 1) factor, an endoplasmic reticulum stress response sensor, which then activates p53 and initiates the apoptotic cascade in the germline [93]. Phosphorylated IRE-1 also activates tumor-necrosis factor (TNF)-receptor-associated factor 2 (TRAF2) which is another apoptosis-initiating factor [94].
Nuclear factor-kappa B and effector molecules in photoaging
Published in Cutaneous and Ocular Toxicology, 2022
Qiang Zhang, Shiyun Qiao, Chunsheng Yang, Guan Jiang
TNF has two receptors, namely, TNF receptor 1 (TNFR1) and TNFR261. TNFR1 is widely expressed, especially in the skin tissues, whereas TNFR2 is only expressed in specific cell types, such as endothelial cells, mesenchymal stem cells, and certain T-cell subpopulations59. TNF receptor-associated factor 2 (TRAF2) is a member of the cytoplasmic adapter and scaffolding proteins commonly expressed in the TRAF family62. TRAF2 has a highly conserved carboxyl-terminal domain called the TRAF domain63. The C-terminal part of the TRAF domain can help TRAF bind directly to the cytoplasmic domain of TNFR263. TRAF2 can also bind to TNFR1 indirectly via the TNFR-associated death domain (TRADD) adaptor protein, a pivotal mediator of TNFR1-mediated signalling transduction59,62. In addition, TNFR1 and TRADD have in their death domain the SXXE/D motifs, which are necessary for the formation of a stable multiprotein complex and the subsequent activation of the IKK/NF-κB pathway56.
The Laboratory Role in anti-TNF Biological Therapy Era
Published in Immunological Investigations, 2020
Valentina Grossi, Francesca Gulli, Maria Infantino, Annunziata Stefanile, Cecilia Napodano, Maurizio Benucci, Krizia Pocino, Francesca Li Gobbi, Arianna Damiani, Antonella Di Pino, Mariangela Manfredi, Mariapaola Marino, Valerio Basile, Gian Ludovico Rapaccini, Umberto Basile
TNF-RI activates anti-apoptotic pathway and is further regulated by the silencer of death domain protein, which inhibits apoptosis (Hehlgans and Pfeffer, 2005; Su-Yin and Cris, 2010). TNF-RII enrolls TNF receptor-associated adaptor factors (TRAF), a family of adaptor proteins which regulate different cellular processes. The exact role of TNF-RII in the regulating pathways has been less investigated, although this may include enhancement of TNF-RI effects through different mechanisms (Juhász et al., 2013): proliferation of CD4+ and CD8 + T-cell subsets, including CD4+ CD25+ regulatory T cells in the periphery (Chen et al., 2007) and the downstream induction of proinflammatory cytokines (Su-Yin and Cris, 2010; Weiss et al., 1997). Moreover, both types of receptors can be cleaved from plasma membranes and released into circulation as soluble forms, able to bind TNF-α. In this way, they act as antagonists, blocking TNF-α signal transduction. TNF-α membrane receptors can activate pro-inflammatory pathways. Furthermore, the tm-TNF-α induces reverse signaling cascades, able to activate anti-inflammatory response (Juhász et al., 2013).
The evolution in our understanding of the genetics of rheumatoid arthritis and the impact on novel drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Filip Machaj, Jakub Rosik, Bartosz Szostak, Andrzej Pawlik
TRAF1 is a gene that encodes TNF receptor-associated factor 1, which is important for the process of the transduction of the signal from TNF receptors. This protein is able to form a complex with TRAF2. The lower expression of TRAF1 might be connected with a more intense inflammatory response [137]. Reducing negative Toll-like receptor signaling by enhancing TRAF1 might become a potential therapeutic option in the near future. TNF receptor superfamily member 1A (CD120a), which is encoded by the TNFRSF1A gene, is another participant in the TNF pathway. Antibodies targeting this protein are also regarded as a therapeutic option in RA. This opinion is seconded by evidence that TNFRSF1A variants influence the TNF signaling pathway in vitro [138]. The usefulness of this novel therapeutic option depends on the effectiveness compared with TNF inhibitors. This opinion is seconded by evidence that TNFRSF1A variants influence the TNF signaling pathway in vitro [138].