The role of danger-associated molecular patterns (DAMPs) in trauma and infections

Sharma, Shefali; Naidu, Gsrsnk

doi:10.21037/jtd.2016.05.22

Cited by 33 publications

(24 citation statements)

References 24 publications

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“…After severe injury and trauma, suppression of immune function may occur due to the desensitization of immune receptors on neutrophils ( 133 ). Trauma/severe injury leads to the release of endogenous danger signals (danger-associated molecular patterns; DAMPs) from necrotic tissue cells that can bind to PRRs on neutrophils ( 134 ). DAMPs, which alert the immune system in response to stress, resemble pathogen-associated molecular patterns (PAMPs) and can bind to their receptors on neutrophils ( 135 ).…”

Section: The Importance Of Neutrophils In Inflammatory Complications mentioning

confidence: 99%

Update on Neutrophil Function in Severe Inflammation

et al. 2018

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Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation.

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Section: The Importance Of Neutrophils In Inflammatory Complications mentioning

confidence: 99%

Update on Neutrophil Function in Severe Inflammation

et al. 2018

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Section: Pparγ Protects Against Cns Injurymentioning

confidence: 99%

“…Inflammatory responses following CNS injury are initiated by damage-associated molecular patterns (DAMPs) that are released from injured tissue (Sharma and Naidu, 2016). High mobility group box 1 is rapidly released by cells undergoing necrotic or pyroptotic cell death (Sharma and Naidu, 2016). High mobility group box 1 is detected in the serum half an hour after 90 min stroke in rodents, and is observed within the first hour after symptom onset in ischemic stroke patients (Liesz et al ., 2015).…”

Section: Pparγ Protects Against Cns Injurymentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair

Cai

Yang

Liu

et al. 2018

Progress in Neurobiology

184

147

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Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries such as stroke by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.

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“…Trauma and sepsis cause tissue injury, resulting in the release of DAMPs that are able to induce a pro-inflammatory signal cascade and the release of pro-inflammatory cytokines such as TNF-α ( 42 ). Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning

et al. 2018

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Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-In silico approach that combines conventional cell culture experiments with machine learning algorithms, we aimed to reduce a significant part of the expensive and time-consuming cell culture experiments and data generation by using computational intelligence (refinement and replacement). Cardiomyocytes exposed to HS showed an activation of the intrinsic apoptosis signal pathway via cytochrome C and the activation of caspase 3 (both p < 0.001). Notably, the exposure of HS resulted in the induction of necroptosis by tumor necrosis factor α and receptor interaction protein 3 (p < 0.05; p < 0.01) and, hence, an increased level of necrotic cardiomyocytes. In conclusion, using this novel Medical-In silico approach, our data suggest (i) that HS induces necroptosis in cardiomyocytes by phosphorylation (activation) of receptor-interacting protein 3, (ii) that HS is a therapeutic target in trauma- or sepsis-associated cardiomyopathy, and (iii) indicate that this proof-of-concept is a first step toward simulating the extent of activated components in the pro-apoptotic pathway induced by HS with only a small data set gained from the in vitro experiments by using machine learning algorithms.

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The role of danger-associated molecular patterns (DAMPs) in trauma and infections

Abstract: Cite this article as: Sharma SK, Naidu G. The role of danger-associated molecular patterns (DAMPs) in trauma and infections.

Cited by 33 publications

References 24 publications

Update on Neutrophil Function in Severe Inflammation

Update on Neutrophil Function in Severe Inflammation

Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair

Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning

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