DAMPs from Cell Death to New Life

Véneréau, Emilie; Ceriotti, Chiara; Bianchi, Marco E.

doi:10.3389/fimmu.2015.00422

Cited by 526 publications

(454 citation statements)

References 115 publications

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“…The relatively rapid occurrence of the HMGB1 release is also compatible with passive release because active secretion usually begins only several hours after proinflammatory stimulation (32). Damaged cells release various factors other than HMGB1 that can function as danger-associated molecular pattern (DAMP) proteins (33). Because we did not attempt to identify secreted proteins in CM in an unbiased manner, it is highly likely Primary cultured microglial cells were incubated with control (CTL) PBS, GLY (120 μL) alone, recombinant HMGB1 (1.0 ng/mL) alone, or a combination of both HMGB1 and GLY for 3 h and then harvested for mRNA extraction.…”

Section: Discussionmentioning

confidence: 99%

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High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Maintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress. HMGB1 rapidly accumulated in the culture medium of OLs exposed to oxygen-glucose deprivation (OGD). This conditioned medium exhibited a protective activity against ischemic OL death that was completely abolished by immunodepletion of HMGB1. Knockdown of HMGB1 or application of glycyrrhizin, a specific HMGB1 inhibitor, aggravated OGD-induced OL death, and recombinant HMGB1 application reduced the extent of OL death in a TLR2-dependent manner. We confirmed that cytosolic translocation of HMGB1 and activation of TLR2-mediated signaling pathways occurred in a focal white matter stroke model induced by endothelin-1 injection. Animals with glycyrrhizin coinjection showed an expansion of the demyelinating lesion in a TLR2-dependent manner, accompanied by aggravation of sensorimotor behavioral deficits. These results indicate that HMGB1/ TLR2 activates an autocrine trophic signaling pathways in OLs and myelin to maintain structural and functional integrity of the white matter under ischemic conditions. white matter stroke | oligodendrocyte | toll-like receptor 2 | HMGB1 | myelination W hite matter in the vertebrate brain is characterized by the presence of myelinated axonal fibers and glial cells, predominantly myelin-producing oligodendrocytes (OLs) (1). The myelin sheath enables rapid communication of neural signals at a millisecond timescale between different parts of the cerebral cortex or different regions of the CNS (2). Therefore, maintaining the integrity of white matter in health and disease, especially of OLs and the myelin sheath, is critical to the performance of a variety of brain functions. Furthermore, recent studies have shown that myelination and OL generation in adulthood are actively regulated in response to neural activities (3, 4), highlighting the potential contribution of white matter plasticity to learning and higher cognitive functions.Ischemic stroke that occurs in the white matter often results in degeneration of OLs and demyelination (5, 6). Consequently, patients with white matter stroke suffer from a wide range of neurological dysfunctions. For example, focal ischemic stroke in the internal capsule may result in severe hemiparesis (7). Furthermore, both cognitive deficits and gait disturbance are hallmarks of Binswanger's subcortical vascular dementia that is the most severe form of white matter stroke (8). How ischemia leads to OL degeneration and demyelination is poorly understood. We previously reported that toll-like receptor 2 (TLR2) expressed in OLs plays a protect...

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Section: Discussionmentioning

confidence: 99%

“…In addition to their proinflammatory roles, recent studies have linked DAMPs to noninflammatory functions such as promoting cellular migration and proliferation, angiogenesis, and tissue repair (33,40). In particular, HMGB1 was shown to contribute to spinal cord regeneration in animal models where spontaneous regeneration occurs (41,42).…”

Section: Discussionmentioning

confidence: 99%

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Later, Matzinger proposed the existence of host molecules (DAMPs) that are released or secreted in response to tissue damage and can initiate and perpetuate an immune response (23,24). Subsequently, it was proven that one of the functions of PRRs is the sensing of tissue damage, and many DAMPs had been identified currently (1)(2)(3)19). Recently, Medzhitov et al proposed that allergic reactions are a component of the host defense system against noninfectious noxious environmental factors, including venoms, noxious xenobiotics, and irritants that can induce tissue damage (25).…”

Section: Discussionmentioning

confidence: 99%

“…Recognizing the ligands of PRRs of either exogenous or endogenous origin subsequently induces an inflammatory response. Numerous DAMPs have been proposed (1,2). However, the ability of many of these compounds to induce sterile inflammation is still under debate because some of them display activities at nonphysiological concentrations, and others are present in high abundance as components of the extracellular matrix (3,4).…”

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confidence: 99%

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Kostarnoy

Gancheva

Lepenies

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the underlying molecular mechanisms are not yet completely understood. Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage. Mincle activation by cholesterol sulfate causes the secretion of a range of proinflammatory mediators, and s.c. injection of cholesterol sulfate results in a Mincle-mediated induction of a severe local inflammatory response. In addition, our study reveals a role of Mincle as a driving component in the pathogenesis of allergic skin inflammation. In a well-established model of allergic contact dermatitis, the absence of Mincle leads to a significant suppression of the magnitude of the skin inflammatory response as assessed by changes in ear thickness, myeloid cell infiltration, and cytokine and chemokine secretion. Taken together, our results provide a deeper understanding of the fundamental mechanisms underlying sterile inflammation.innate immunity | sterile inflammation | allergy | Mincle | cholesterol sulfate

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“…In addition, damaged-molecular-patterns (DAMPs) are molecules that have a physiological role inside the cell, but acquire additional functions when they are exposed to the extracellular environment: they alert the body about danger, stimulate an inflammatory response, and finally promote the regeneration process. Beside their passive release by dead cells, some DAMPs can be secreted or exposed by living cells undergoing a life-threatening stress [20]. DAMPs could target the cytokines synthesis during hypoxic condition.…”

Section: Discussionmentioning

confidence: 99%