CD14-dependent alterations in c-Jun expression in the liver after burn injury1

Cho, Ki-Ho; Adamson, Lee; Jeong, Jayoung; Crivello, Sicily D.; VanHook, T.; Palmieri, Tina L; Greenhalgh, David G.

doi:10.1016/j.jss.2004.07.007

Cited by 13 publications

(9 citation statements)

References 34 publications

(30 reference statements)

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“…Although CD14 has been recognized as an important inflammation mediator in burn-associated pathological responses in multiple organs including the liver (11,13,14), lung (14), skin (43), and adrenal gland (12), its role in myocardium and myocardial mitochondrial function has not been elucidated. A recent study from our laboratory suggests that burn injury significantly elevated CD14 expression in the heart tissue and in cardiomyocytes (5).…”

Section: Discussionmentioning

confidence: 99%

“…However, most studies to date have focused on the effects of total intracellular ROS. We hypothesize that burn injury produces functional defects of myocardial mitochondria and causes overproduction of mitochondrial ROS (mtROS), leading to a cascade of molecular events that generate cardiac contractile dysfunction.CD14, a member of the toll-like receptor 4 (TLR4) signalosome, is involved in the regulation of postburn pathogenic responses in distant organs such as the liver (11,13,14), lung (14), skin (43), and adrenal gland (12). Consistently, recent clinical research has correlated genetic variations within the TLR4 gene with the risk of post-trauma organ failure (4, 41).…”

mentioning

confidence: 99%

“…CD14, a member of the toll-like receptor 4 (TLR4) signalosome, is involved in the regulation of postburn pathogenic responses in distant organs such as the liver (11,13,14), lung (14), skin (43), and adrenal gland (12). Consistently, recent clinical research has correlated genetic variations within the TLR4 gene with the risk of post-trauma organ failure (4, 41).…”

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confidence: 99%

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Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes

Zang

Maass

Wigginton

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Studies from animal models suggest that myocardial mitochondrial damage contributes to cardiac dysfunction after burn injury. In this report, we used an ex vivo model of primary cardiomyocyte culture to investigate the mechanisms of burn-induced mitochondrial impairment. Briefly, blood serum was collected from Sprague-Dawley (SD) rats subjected to 40% total body surface area burn and added (10% vol/vol) to primary cardiomyocytes prepared from SD rats. The effect of the burn serum on mitochondrial function and membrane integrity in the myocytes was analyzed. Exposure of myocytes to burn serum doubled the mitochondrial membrane damage measured by two independent assays. This treatment also significantly elevated mitochondrial oxidative stress, indicated by a more than 30% increase in lipid oxidation. Downregulation of mitochondrial antioxidant defense was also evident since the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were reduced by about 30% and 50%, respectively. Burn serum also induced deficiency of mitochondrial metabolism, indicated by a 30% decrease in the activity of cytochrome c oxidase. These mitochondrial dysfunctions appear to be generated by oxidative stress because burn serum induced a significant increase of mitochondrial oxygen species (mtROS) in cardiomyocytes, and pretreatment of cardiomyocytes with the antioxidant N-acetyl-cysteine prevented the mitochondrial damages induced by burn serum. Remarkably, the increase in mtROS was abolished by an antibody-mediated blockade of CD14. Furthermore, burn injury-induced mitochondrial damage in cardiomyocytes was prevented in CD14 knockout mice. Taken together, these data suggested that burn injury produces CD14-dependent mitochondrial damage via oxidative stress in myocardium.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes

Zang

Maass

Wigginton

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…We recently identified a number of putative transcription factors of cytokines and chemokines which have been significantly altered following burn injury or sepsis [15]. Some of these transcription factors identified such as NFKB (or NF-κβ), STAT and CEBP have been already well studied in literature and shown to be activated by burn and sepsis in various tissues [13, 17–19]. We further showed that there are also other putative transcription factors including ETS1, SP1, GATA, and VTBP which might play important roles during the inflammation by regulating the production of a number of cytokines and chemokines[15].…”

Section: Introductionmentioning

confidence: 99%

Long-term dynamic profiling of inflammatory mediators in double-hit burn and sepsis animal models

et al. 2012

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Burn injuries together with its subsequent complications, mainly bacterial infections originating from gastrointestinal tract, activate the host immune system through stimulation of a series of local and systemic responses, including the release of inflammatory mediators. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to analyze animal models of burn and sepsis. In this study, we analyzed the long term profiles of cytokines and chemokines in rat models which received burn injury followed two days later by cecal ligation and puncture (CLP) to induce sepsis and were sacrificed at different time points within 10 days (0, 1, 2, 3, 4, 7 and 10 days). It was observed that MCP-1 concentrations were elevated in all animal models following the burn injury or CLP treatment. IP-10 concentration was persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was also increased following the burn injury and CLP. It was elucidated that, in more severe injury model which received both burn and CLP treatments, GMCSF and MIP-1α (chemokines), IL-1α (a pro-inflammatory cytokine) and IL-6 (exhibiting both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th days, which might be to protect the host system from the subsequent complications caused by burn and sepsis. In order to elucidate critical regulatory interactions, putative transcription factors of the inflammatory mediators which have been significantly changed following the injuries were further identified by analyzing the conserved regions of the promoters of cytokines and chemokines. In conclusion, the long term profiles of the inflammatory mediators were profoundly characterized in this study to gain a comprehensive understanding of inflammatory mediators’ behaviors in various injury models.

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“…Animals studies have shown that hyperactive Kupffer cells can cause hepatic damage after many types of injury, including hemorrhagic pancreatitis [77], trauma and sepsis [78], as well as burns [79]. Burn injury causes a transient induction of CD14 in Kupffer cells, leading to enhanced TLR4 signaling and cytokine production in mice [80]. This is supported by work with CD14 knockout mice and TLR4 defective animals implicating LPS as the initial inducing agent associated with acute phase responses (APR) in the liver after burn [81].…”

Section: Intrahepatic Mechanismsmentioning

confidence: 99%

Alcohol Modulation of the Postburn Hepatic Response

Chen

Carter

Curtis

et al. 2017

Journal of Burn Care & Research

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The widespread and rapidly increasing trend of binge drinking is accompanied by a concomitant rise in the prevalence of trauma patients under the influence of alcohol at the time of their injury. Epidemiologic evidence suggests up to half of all adult burn patients are intoxicated at the time of admission and the presence of alcohol is an independent risk factor for death in the early stages post burn. As the major site of alcohol metabolism and toxicity, the liver is a critical determinant of post burn outcome and experimental evidence implies an injury threshold exists beyond which burn-induced hepatic derangement is observed. Alcohol may lower this threshold for post burn hepatic damage through a variety of mechanisms including modulation of extrahepatic events, alteration of the gut-liver axis, and changes in signaling pathways. The direct and indirect effects of alcohol may prime the liver for the second-hit of many overlapping physiologic responses to burn injury. In an effort to gain a deeper understanding of how alcohol potentiates post burn hepatic damage, we summarize possible mechanisms by which alcohol modulates the post burn hepatic response.

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CD14-dependent alterations in c-Jun expression in the liver after burn injury1

Cited by 13 publications

References 34 publications

Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes

Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes

Long-term dynamic profiling of inflammatory mediators in double-hit burn and sepsis animal models

Alcohol Modulation of the Postburn Hepatic Response

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