Detection of Membrane Associated Thioredoxin on Human Cell Lines

Wollman, Emmanuelle E.; Kahan, A; Fradelizi, D

doi:10.1006/bbrc.1996.6015

Cited by 31 publications

(18 citation statements)

References 14 publications

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“…It remains to be confirmed whether dl-CD40 homodimers assemble into DRM microdomains under the action of a common accessory molecule such as thioredoxin or a protein-disulfide isomerase. These enzymes are present at the plasma membrane, particularly in DRM fractions, and in the cytoplasmic and nuclear compartments of various cells (17), including human B cells (36,37). Further study is undertaken to assess whether any specific disulfide isomerase is required during dl-CD40 homodimer formation.…”

Section: Discussionmentioning

confidence: 99%

Requirement of Oxidation-dependent CD40 Homodimers for CD154/CD40 Bidirectional Signaling

Reyes‐Moreno

Sharif-Askari

Girouard

et al. 2007

Journal of Biological Chemistry

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It is well established that the CD154/CD40 interaction is required for T cell-dependent B cell differentiation and maturation. However, the early molecular and structural mechanisms that orchestrate CD154 and CD40 signaling at the T cell/APC contact site are not well understood. We demonstrated that CD40 engagement induces the formation of disulfide-linked (dl) CD40 homodimers that predominantly associate with detergent-resistant membrane microdomains. Mutagenesis and biochemical analyses revealed that (a) the integrity of the detergentresistant membranes is necessary for dl-CD40 homodimer formation, (b) the cytoplasmic Cys 238 of CD40 is the target for the de novo disulfide oxidation induced by receptor oligomerization, and (c) dl-CD40 homodimer formation is required for CD40-induced interleukin-8 secretion. Stimulation of CD154-positive T cells with staphylococcal enterotoxin E superantigen that mimics nominal antigen in initiating cognate T cell/APC interaction revealed that dl-CD40 homodimer formation is required for interleukin-2 production by T cells. These findings indicate that dl-CD40 homodimer formation has a physiological role in regulating bidirectional signaling.Primary immune responses are initiated by specific physical interactions between antigen-specific T cells and antigen-presenting cells (APCs), 4 resulting in bidirectional signal transducing events that modulate cell functions (1). Various cytokine and co-stimulatory receptors provide the input to direct these processes. Elucidating the mechanisms underlying the regulation of cell/cell interactions is thus crucial for further understanding the immunological responses and improving therapeutic strategies aimed at treating cell/cell interaction-mediated human diseases. CD154 and CD40 molecules are pairs of ligand/receptor that belong to the tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamily and that play a pivotal role in cell/cell interactions (1). In B cells, the CD154/CD40 interaction is responsible for clonal expansion, germinal center formation, isotype switching, affinity maturation, and rescue from surface Ig-induced apoptosis. In nonhematopoietic cells, ligation of CD40 with CD154 enhances the secretion of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-␣. The absence or disruption of the CD154/CD40 pathway leads to a severe perturbation of the immune system, for example, in X-linked immunodeficiency with hyper-IgM (1). This observation has been confirmed using CD154 and CD40 knock-out mice (2, 3). Like most ligand/receptor pairs, the CD154/CD40 interaction leads to a bidirectional signal that leads to proliferation and IL-2 production (3) as well as various cellular events that modulate T cell functions.Because CD40 has no kinase domain, the transmission of its intracellular signals passes via the recruitment of several adaptor proteins, such as Jak3 and TNFR-associated factor (TRAF) proteins, to specific domains in its cytoplasmic tail. This results in the activation of members of the Src kinase family (such as Ly...

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Section: Discussionmentioning

confidence: 99%

Requirement of Oxidation-dependent CD40 Homodimers for CD154/CD40 Bidirectional Signaling

Reyes‐Moreno

Sharif-Askari

Girouard

et al. 2007

Journal of Biological Chemistry

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“…Trx-maintained reducing microenvironments facilitate the proliferation of T lymphocytes during antigen-specific interactions with dendritic cells (DCs), and they buffer apoptosis in primary T lymphocytes and Jurkat T cells (4,72). Trxs are expressed in primary T lymphocytes and T-cell lines, mainly upon mitogenic stimulation in the former (150,169,187), and Trx is particularly prominent in T lymphocytes of the intestinal lamina propria. These cells expressed more Trx than peripheral blood T cells (PBTs), and they produce more proinflammatory cytokines in response to activation stimuli (161).…”

Section: A Role For S-nitrosylation In T-cell Activationmentioning

confidence: 99%

Nitrosothiols in the Immune System: Signaling and Protection

Hernansanz-Agustín

Izquierdo-Álvarez²,

García-Ortiz³

et al. 2013

Antioxidants & Redox Signaling

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“…Upon cellular activation, Trx expression is up-regulated and the protein may be either translocated to the nucleus or secreted to the extracellular environment (4,5,22,29,31,32,36,40,41,43,52,55,63,71,74). Although several different cell types have been screened for Trx80 content, the number of cells producing Trx80 is quite limited.…”

Section: Production Secretion and Cellular Localization Of Trx80mentioning

confidence: 99%

Truncated Thioredoxin: Physiological Functions and Mechanism

Pekkari

Holmgren

2004

Antioxidants & Redox Signaling

103

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Human cytosolic thioredoxin (Trx), which is the 12-kDa protein disulfide reductase with the Cys-Gly-Pro-Cys active site and a key component of cellular redox biochemistry and regulation, acts as cocytokine upon leaderless secretion. A 10-kDa C-terminally truncated thioredoxin (Trx80) comprising the 80 or 84 N-terminal amino acids is also secreted and present in plasma, where it originally was purified and identified as eosinophilic cytotoxicity enhancing factor. Recombinant Trx80 was discovered to be a potent mitogenic cytokine that stimulates growth of resting human peripheral blood mononuclear cells (PBMC) in a synthetic medium, an effect that Trx lacks. Trx80 is very different from Trx because it is a dimer lacking reductase activity and the cytokine activity is not dependent on the Cys residues of the Trx active-site motif. The primary targets of Trx80 in PBMC are monocytes that are activated to proliferate and increase expression of CD14, CD40, CD54, and CD86. Trx80 induces secretion of interleukin (IL)-12 in CD40+ monocytes from PBMC. Trx80 and IL-2 together were strongly synergistic to induce secretion of interferon-gamma in PBMC. Trx80 is a potent cytokine for monocytes directing the immune system to a Th1 response via IL-12 production.

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Detection of Membrane Associated Thioredoxin on Human Cell Lines

Cited by 31 publications

References 14 publications

Requirement of Oxidation-dependent CD40 Homodimers for CD154/CD40 Bidirectional Signaling

Requirement of Oxidation-dependent CD40 Homodimers for CD154/CD40 Bidirectional Signaling

Nitrosothiols in the Immune System: Signaling and Protection

Truncated Thioredoxin: Physiological Functions and Mechanism

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