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Tumor Necrosis Factor
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Peter G. Brouckaert, Claude Libert
Both receptors can shed their extracellular domain and give rise to soluble TNF-binding proteins. The receptors can be found in human serum and urine, and can inhibit TNF effects on target cells. Although lymphotoxin binds to both cellular receptors, it binds only very slightly or not at all to the soluble binding proteins.19
Macrophage-Lymphocyte Interactions in Tumor Recognition and Response
Published in Gloria H. Heppner, Amy M. Fulton, Macrophages and Cancer, 2019
James L. Urban, Jay L. Rothstein, Hans Schreiber
Although lymphotoxin and TNF only share about 30% sequence homology,24,27 they compete for binding to the same cellular receptor suggesting that they may share common cellular effector pathways.28 In order to determine whether the Mϕ-resistant variants had also become resistant to lymphotoxin, we compared the sensitivity of Mϕ-resistant variants and the parental 1591 tumor to the two recombinant cytotoxic proteins. Figure 10 shows that the two proteins had an identical effect on the parental 1591 tumor and both failed to exert a cytotoxic effect on two Mϕ-resistant variants. Although the gene from which the recombinant lymphotoxin had been produced was originally isolated from a lymphoblastoid B cell line,24 it is now clear that only nonmalignant activated T cells express this gene and secrete its product.38 In unpublished experiments with Drs. Gibb Otten and Frank Fitch from the University of Chicago, we have found that a helper T cell clone,29 when activated in an I-Ak-restricted antigen-specific way, will secrete lymphotoxin with marked cytotoxic activity toward the TNF-sensitive 1591 parental tumor. In addition, this lymphotoxin had precisely the same reactivity pattern as TNF in that it did not affect the 1591 variants resistant to recombinant murine or human TNF. Therefore, this natural T helper cell-derived lymphotoxin appears to behave similarly to the recombinant lymphotoxin in reactivity towards the parental and the variant tumor cell lines.
Pathophysiology of Atopic Dermatitis and Atopiform Dermatitis
Published in Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld, Atopic Dermatitis and Eczematous Disorders, 2014
Th1 lymphocytes produce interferon-γ (IFN-γ), lymphotoxin, and tumor necrosis factor-α (TNF-α) but not IL-4, -5, and -13, and are involved in so-called ‘cellular immunity.’ Th2 cells secrete IL-4, -5, and -13. Certain Th1 or Th2 cytokines can further polarize immune responses by their effect on precursor T cells. Thus IFN-γ can inhibit differentiation of Th2 cells and IL-4 can inhibit Th1 polarization (Fig 6.5). Many circulating lymphocytes in humans express a combination of Th1 and Th2 cytokines and are referred to as Th0 cells.
Genetic Variation on TNF/LTA and TNFRSF1A Genes is Associated with Outcomes of Hepatitis C Virus Infection
Published in Immunological Investigations, 2021
Ming Yue, Peng Huang, Chunhui Wang, Haozhi Fan, Ting Tian, Jingjing Wu, Fan Luo, Zuqiang Fu, Xueshan Xia, Ping Zhu, Jun Li, Yaping Han, Yun Zhang, Wei Hou
As a relatively significant member of the TNFSF, tumor necrosis factor (TNF) as well as lymphotoxin alpha (LTA) are important cytokines produced by activation of macrophages and T cells after injury to tissue (Dostert et al. 2019). TNF and LTA share the same membrane receptors, including TNFRSF member 1A (TNFRSF1A) and TNFRSF member 1B (TNFRSF1B). These membrane receptors each exert different regulatory effects by activating different inflammatory responses, and differentially affect proliferation, and differentiation of immune cells (Baud and Karin 2001; Vielhauer and Mayadas 2007). Recent research has indicated that TNF and LTA can enhance HCV entry by inducing the activation of nuclear factor κ-light-chain-enhancer in activated B cells and enhances entry by way of inducing activation of myosin light chain kinase signaling pathways thereby reducing tight junction integrity of hepatocytes (Miao et al. 2017). Moreover, binding of the HCV core protein to the cytoplasmic domain of TNFRSF1A, particularly to the “death domain”, may act to either hinder or promote cell death during HCV infection (Getachew et al. 2004). Additional research has indicated that the levels of serum TNF and soluble TNFRSF1A were elevated in patients with chronic hepatitis C and indicated that high levels of TNF were associated with poor prognosis and low responses to interferon based treatment (Grebely et al. 2015; Larrea et al. 1996; Tilg et al. 1992).
Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats
Published in mAbs, 2020
Ami Miller, Stephen Carr, Terry Rabbitts, Hanif Ali
Humira, Humira scFv-TD, and Humira scFv preparations were immobilized onto a CM5 sensor chip (GE Healthcare) using standard amine coupling on a Biacore T200 Instrument (GE Healthcare). The surfaces were activated for 5 min with 0.2 M N-ethyl-N-(dimethylaminopropyl) carbodiimide hydrochloride and 0.05 M N-hydroxysuccinimide at 20 μl/min, before the proteins were injected at 20 μg/ml in 10 mM sodium acetate, pH 4.5. The surfaces were blocked with a 5-min injection of 1 M ethanolamine, pH 8.5 at 20 µl/min. The immobilization levels of Humira, Humira scFv-TD, and Humira scFv were 16500, 8400, and 1100 RU, respectively. The running buffer HBS-EP (GE Healthcare), comprising 10 mM HEPES, pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.005% v/v Surfactant P20. Recombinant Human TNF (ab9649, Abcam) was diluted in running buffer to a concentration of 57 nM. For each analysis, three start up cycles were performed before a single-cycle kinetics high-performance run was implemented with a contact time of 30 sec and a dissociation time of 300 sec, at a flow rate of 30 µl/min. The sensorgrams were double referenced with an empty reference cell that had been through the same activation and deactivation cycles, and a buffer only injection. Binding data were collected at 37°C. The BIAevaluation 2.1 software (GE Healthcare) was used to analyze the data. Curve fitting to the association and dissociation phases was used to calculate the on and off rate and the Kd of the interaction was calculated from these values. The experiment was repeated with recombinant human lymphotoxin alpha1/beta2 (R&D Systems), at a concentration of 87 nM.
Polymorphisms of the TNF, LTA, and TNFRSF1B genes are associated with onsets of menarche and menopause in US women of European ancestry
Published in Annals of Human Biology, 2021
Volodymyr Dvornyk, Mikhail Churnosov, Hong-Wen Deng
The tumour necrosis factor (TNF), lymphotoxin alpha (LTA) and TNF receptor superfamily member 1B (TNFRSF1B) genes are members of the tumour necrosis factor and its receptor superfamilies, which have been implicated in multiple cellular processes, including cell–cell signalling, cell proliferation and apoptosis, in many tissues. There is ample evidence suggesting the contribution of these genes to various health problems associated with AM and ANM, such as osteoporosis (Khosla 2013), obesity and breast cancer (To et al. 2013; Rose and Vona-Davis 2014), and cardiovascular diseases (Pawluk et al. 2020), to name a few. Given the above data, we tested the hypothesis that the TNF, LTA and TNFRSF1B genes may be associated with AM and ANM.