Gene Expression, Cytokine and Enzyme Activation in the Liver after Burn Injury

Nishiura, Teruhiro; Nishimura, Toshiaki; deSerres, Suzan; Nakagawa, Tomoyuki; Brenner, Dirk; Meyer, Andreas

doi:10.1097/00004630-199801001-00206

Cited by 6 publications

(9 citation statements)

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“…Clinical studies have shown that liver dysfunction and damage are essential for survival in critically ill and severely burned patients [1,2]. Various cellular and molecular interactions such as neutrophil and macrophage activation, mitochondrial dysfunction oxygen radical, cytokine overproduction, depletion of glutathione, may be involved in the processes [3][4][5][6]. These complex mechanisms cause liver dysfunction, alteration of hepatic parenchyma and eventually cell death (apoptosis).…”

Section: Introductionmentioning

confidence: 99%

Melatonin modulates the expression of Bcl-2 family proteins in liver after thermal injury in rats

Bekyarova¹,

Tzaneva²,

Hristova³

2013

ABB

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Melatonin, the principal secretory product of the pineal gland, functions as a potent antioxidant and free radical scavenger. Additionally, the antiapoptotic effect of melatonin has been observed both in vivo and in vitro. The aim of this study was to investigate the protective effects of melatonin against burn-induced injury in rat liver and whether these changes were associated with oxidative stress and changes in the expression of apoptosis related genes Bcl-2 and Bax. Melatonin (10 mg/kg, i.p.) was applied immediately after 30% of total body surface area (TBSA) burns of male Wistar rats. Malondialdehyde (MDA) as marker of oxidative stress and tumor necrosis factor (TNF-α) as inflammatory marker were assayed by biochemical methods. The hepatic apoptosis related genes Bcl-2 and Bax using light immunоchistochemistry were investigated, too. Hepatic TNF-α and MDA levels were increased significantly following severe burn. Thermal trauma increased the Bax expression without any changes of anti-apoptotic Bcl-2 protein in sinusoidal endothelial cells (SECs) of burn-treated animals compared with the control group animals as well as elevated ratio Bax/Bcl-2 suggesting the susceptibility of these cells to apoptosis. Melatonin significantly decreased the MDA and TNF-α levels in the liver tissue. It decreased also expression of Bax, increased expression of Bcl-2 and reduced Bax/Bcl-2 ratio. In conclusion, experimental data show that melatonin modulates the expression of Bcl-2 family proteins by increasing anti-apoptotic Bcl-2, inhibits apoptosis and restricts the burn-induced damage.

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Section: Introductionmentioning

confidence: 99%

Melatonin modulates the expression of Bcl-2 family proteins in liver after thermal injury in rats

Bekyarova¹,

Tzaneva²,

Hristova³

2013

ABB

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“…Being central role in metabolism and host defense mechanisms, the liver is thought to be a major organ responsible for the initiation of multiple organ failure in patients with major burns [3]. Proinflammatory cytokines such as tumor necrosis factor (TNF) -α and interleukin (IL)-1β have been demonstrated to be the two most important cytokines in the early phase of burns and play an important role in producing hepatocelluar dysfunction [4].…”

Section: Introductionmentioning

confidence: 99%

High-Mobility Group Box-1 Induces Proinflammatory Cytokines Production of Kupffer Cells through TLRs-Dependent Signaling Pathway after Burn Injury

Chen

Sun²,

Guo³

et al. 2012

PLoS ONE

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Kupffer cells (KCs) were a significant source of cytokine release during the early stage of severe burns. High mobility group box protein 1 (HMGB1) was recently identified as a new type of proinflammatory cytokine. The ability of HMGB1 to generate inflammatory responses after burn trauma has not been well characterized. KCs were isolated from sham animals and rats with a 30% full-thickness burn, and then were stimulated with increasing concentrations of HMGB1. The levels of Tumor necrosis factor (TNF)-α and interleukin (IL)-1β in culture supernatant were measured by enzyme-linked immunosorbent assay. Northern blot analysis was performed to detect the expressions of TNF-α and IL-1β mRNAs. The activities of p38 MAPK and JNK (by Western blot analysis) as well as NF-κB (by EMSA) in KCs were also examined. As a result, HMGB1 in vitro upregulated expressions of TNF-α and IL-1β of KCs in a dose-dependent manner, and HMGB1 promoted KCs from burn rats to produce significantly more TNF-α and IL-1β proteins than those from sham animals. After harvested from burn rats, KCs were pre-incubated with anti-TLR2 or anti-TLR4 antibody prior to HMGB1 administration. HMGB1 exposure not only significantly increased expressions of TNF-α and IL-1β mRNAs in KCs from burn rats, but also enhanced activities of p38 MAPK, JNK and NF-κB. However, these upregulation events were all reduced by pre-incubation with anti-TLR2 or anti-TLR4 antibody. These results indicate that HMGB1 induces proinflammatory cytokines production of KCs after sever burn injury, and this process might be largely dependent on TLRs-dependent MAPKs/NF-κB signal pathway.

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“…No adverse reaction related to the test drug was observed. Although the laboratory examination of some patients appeared to be normal to a certain extent, all abnormality appeared before treatment, which might have been caused by the burn itself 7–9 . With the progression of burn, the measurements of the laboratory examination were gradually improved and finally became normal.…”

Section: Discussionmentioning

confidence: 98%

A multicenter clinical trial of recombinant human GM‐CSF hydrogel for the treatment of deep second‐degree burns

Zhang

Chen

Han

2009

Wound Repair Regeneration

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Wound healing is a complex and dynamic biological process. The efficacy and safety of a recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) hydrogel to promote deep-second-degree burn wound healing is evaluated in this study. In this multicenter, randomized, double-blind, and placebo-controlled clinical trial, 90 patients with deep second-degree burns were randomly assigned into two groups. Complete healing time and percentage of wound healing at different time points were observed and side effects were recorded. A statistically significant difference was noted at each time point (p<0.01). No side effects were observed. These results suggest that rhGM-CSF hydrogel can significantly accelerate deep second-degree burn wound healing and is considered to be safe.

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Gene Expression, Cytokine and Enzyme Activation in the Liver after Burn Injury

Cited by 6 publications

References 0 publications

Melatonin modulates the expression of Bcl-2 family proteins in liver after thermal injury in rats

Melatonin modulates the expression of Bcl-2 family proteins in liver after thermal injury in rats

High-Mobility Group Box-1 Induces Proinflammatory Cytokines Production of Kupffer Cells through TLRs-Dependent Signaling Pathway after Burn Injury

A multicenter clinical trial of recombinant human GM‐CSF hydrogel for the treatment of deep second‐degree burns

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