Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

Véneréau, Emilie; Casalgrandi, Maura; Schiraldi, Milena; Antoine, Daniel J.; Cattaneo, Angela; Marchis, Francesco De; Liu, Jaron; Antonelli, Antonella; Preti, Alessandro; Raeli, Lorenzo; Shams, Sara Samadi; Yang, Huan; Varani, Luca; Andersson, Ulf; Tracey, Kevin J.; Bachi, Ángela; Uguccioni, Mariagrazia; Bianchi, Marco E.

doi:10.1085/jgp1403oia3

Cited by 134 publications

(288 citation statements)

References 10 publications

(12 reference statements)

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“…The partially oxidized isoform in contrast preferentially activates the Toll-like receptor-4 (TLR4) with downstream chemokine and cytokine release. [34][35][36] The terminally oxidized sulfonate isoform appears even less able to attract leukocytes or to elicit cytokines, even if it maintains the ability to modulate neutrophil integrin transactivation and degranulation. 37 HMGB1 is weakly expressed in healthy muscles.…”

Section: Unique Immune Privileges Of the Skeletal Musclementioning

confidence: 99%

Cell death, clearance and immunity in the skeletal muscle

et al. 2016

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Section: Unique Immune Privileges Of the Skeletal Musclementioning

confidence: 99%

Cell death, clearance and immunity in the skeletal muscle

et al. 2016

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“…58 As HMGB1 is an intrinsic sensor of oxidative stress, 59 the immunomodulatory properties of HMGB1 might be determined by its redox status. 60,61 Indeed, reduced HMGB1 production from dying cells was shown to trigger the immunogenic DCs, whereas oxidized HMGB1 during apoptosis fails. 51 As the extracellular space is usually oxidative under physiological conditions but is unpredictably variable under pathogenic conditions, 62 the unstable redox status of the tumor microenvironment might account for these inconsistent findings.…”

Section: Hmgb1mentioning

confidence: 99%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases.

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“…Moreover, during apoptotic cell death, critical cysteine residues of HMGB1 can become oxidized due to caspase-dependent production of reactive oxygen species, preventing HMGB1 binding to RAGE as well as the TLR receptors. 28,29 Thus, HMGB1 released after staurosporine or sodium azide-induced apoptotic cell death may be biologically inactive. Whether other means of inducing apoptosis, for example, immunogenic apoptosis, will result in a higher release of biologically active HMGB1 needs to be determined.…”

Section: Migration Of Msc Towards Recombinant Hgf Was Inhibitedmentioning

confidence: 99%

“…This implies that HMGB1 released by necrotic cells may be in its all-thiol form, which is required for RAGE binding. 28,29 In addition, RAGE dependency of its migratory effect suggests that HMGB1 by itself acts as a chemoattractant and does not require the formation of complexes with CXCL12, because these have been reported to signal via C-X-C chemokine receptor type 4 (CXCR4). 32,41 This conclusion is further supported by the under-agarose migration assay employed here: when recombinant HMGB1 was used as a target, only a stable gradient of HMGB1 could form, along which the cells could migrate, whereas the concentration of CXCL12, if produced by the monocytes and iDC, would have been highest at the site of these cells.…”

Section: Migration Of Msc Towards Recombinant Hgf Was Inhibitedmentioning

confidence: 99%

“…[23][24][25] Moreover, HMGB1 is a prototypic damageassociated molecular pattern passively released from necrotic cells. 26 Although it may be released from apoptotic cells as well, 27 it appears to be preferentially retained in apoptotic bodies because of enhanced chromatin binding 26 and to be inactive due to oxidization of the crucial cysteine residues 23, 45 and 106, 28,29 which is critical for the tolerogenic nature of apoptotic cell death. Either secreted or passively released from necrotic cells, HMGB1 exerts its effects via the receptor of advanced glycation end products (RAGE) 30 and the tolllike receptors TLR-2 and TLR-4, 31 and may form complexes with chemokines-such as chemokine C-X-C motif ligand 12 (CXCL12), enhancing their activity.…”

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Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

et al. 2015

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Tissue damage due to apoptotic or necrotic cell death typically initiates distinct cellular responses, leading either directly to tissue repair and regeneration or to immunological processes first, to clear the site, for example, of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have regenerative capacity, whereas monocytes and iDC have a critical role in inflammation and induction of immune responses, including autoimmunity after tissue damage. Here, we investigated the influence of apoptotic and necrotic cell death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors differentially regulating these migratory responses. MSC, but not monocytes or iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic cell death resulted in HGF production and HGF-mediated migration of MSC towards the apoptotic targets. In contrast, HMGB1 was predominantly released by the necrotic cells and mediated recruitment of monocytes and iDC via the receptor of advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death differentially regulates recruitment of either MSC or monocytes and iDC through HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in determining tropism after tissue injury.

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Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

Cited by 134 publications

References 10 publications

Cell death, clearance and immunity in the skeletal muscle

Cell death, clearance and immunity in the skeletal muscle

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

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