Gene Expression and Cytokine and Enzyme Activation in the Liver After a Burn Injury

Nishiura, Teruhiro; Nishimura, Toshiaki; deSerres, Suzan; Godfrey, Virginia; Bradham, Cynthia A.; Nakagawa, Takao; Brenner, David A.; Meyer, Anthony A.

doi:10.1097/00004630-200021020-00009

Cited by 21 publications

(8 citation statements)

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“…As shown in Figure 4, 30 min post burn, TNF-α and IL-6 were readily detected in circulating WBCs, as well as burned skin. As reported, the rapidness was accompanied by burn injury-induced activation of NF-kB within 30 min and significantly increased IL-6 production in lung tissue (35). Noticeably, globally inflammatory reactions were rapidly initiated by burn injury.…”

Section: Discussionsupporting

confidence: 68%

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

Xiao

et al. 2017

Mol Med

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Previously, we showed that an oligodeoxynucleotide (ODN) with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, its underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the sequence of AAAG ODN is in consensus with the interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether AAAG ODN could attenuate burn injury-induced systemic inflammatory responses by inhibiting the IRF5 pathway. Using a mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the lifespan of the mice, decreased the expression of IRF5 in the injured skin, reduced the production of TNF-α and IL-6 in the blood and injured skin, and attenuated the ALI. These effects were correlated with AAAG ODN-mediated inhibition of nuclear translocation of IRF5. The data suggest that AAAG ODN could act as a cytoplasmic decoy capable of interfering the function of IRF5 and be developed as a drug candidate for the treatment of inflammatory diseases. online address: http://www.molmed.org

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Section: Discussionsupporting

confidence: 68%

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

Xiao

et al. 2017

Mol Med

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“…Melatonin administration down-regulates hepatic NF-kB expression and TNF-a level and attenuates liver damage . Plasma AST activity important pathophysiological mechanism in liver injury (24,25). Liver is not only a major source of inflammatory mediator cytokines and free radicals but is also a target organ for their damaging effect (6,19).…”

Section: Discussionmentioning

confidence: 99%

“…The oxygen and nitrogen-based reactants contribute to the activation of lipid peroxidation, protein oxidation and DNA damage in the liver after burns when its antioxidant defense is reduced (26). This mechanism involves NF-kB induction leading to cytokine-induced inflammation (24,25). High TNF-a levels activate cell-death pathways and promote the production of reactive oxygen species and expression of other inflammatory factors such as IL-6, ICAM-l, NO and thus hepatic injury (7,21).…”

Section: Discussionmentioning

confidence: 99%

Melatonin Protection against Burn-Induced Hepatic Injury by Down-Regulation and Nuclear Factor Kappa B Activation

Bekyarova

Apostolova

Kotzev

2012

Int J Immunopathol Pharmacol

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Melatonin exhibits a wide variety of biological activity including antioxidant and anti-inflammatory effects. We have previously reported its protective effect on hepatic oxidative hepatic injury in burns. In this study, we investigated the role of nuclear factor kappa B (NF-kB) in melatonin-mediated protection against liver injury by using the burned-rat model. Melatonin (N-acetyl-5-methoxytriptamin, 10mgl kg (-1), Lp.) was administered immediately and 12 hours after thermal skin injury. Hepatic NF-kB expression was determined by Western blotting. TNF-a level in liver homogenate was quantified using enzyme-linked immunosorbent assay (ELISA) kit. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver injury at the 24 th hour after burns. Thermal skin injury caused significant elevation of hepatic NF-kB expression by 48%, TNF-a level by 55% and plasma AST and ALT activities by 2-and 3-fold, respectively, in comparison with normal control rats. Treatment with melatonin decreased significantly elevated hepatic NF-kB activity and TNF-a, maintaining the levels close to the control values Melatonin suppressed the elevation of plasma AST and ALT activities (p

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“…A study from our group (15) showed an increase of NF-κB proteins in hepatocytes harvested from rats that received a 40% burn injury. Nishiura et al (16) showed activation of the NF-κB pathway within 30 min after burn injury in mice. The liver plays central roles in metabolism, inflammation and acute response to trauma or injury and is pivotal to patient survival and recovery.…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia Exacerbates Burn-Induced Liver Inflammation via Noncanonical Nuclear Factor-κB Pathway Activation

Kulp

Tilton

Herndon

et al. 2012

Mol Med

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Hyperglycemia and inflammation are hallmarks of burn injury. In this study, we used a rat model of hyperglycemia and burn injury to investigate the effects of hyperglycemia on inflammatory responses in the liver. Hyperglycemia was induced in male Sprague-Dawley rats with streptozotocin (STZ) (35-40 mg/kg), followed by a 60% third-degree scald burn injury. Cytokine levels (by multiplex, in cytosolic liver extracts), hormones (by enzyme-linked immunosorbent assay [ELISA], in serum), nuclear factor (NF)-κB protein deoxyribonucleic acid (DNA) binding (by ELISA, in nuclear liver extracts) and liver functional panel (using VetScan, in serum) were measured at different time points up to 7 d after burn injury. Blood glucose significantly increased after burn injury in both groups with different temporal patterns. Hyperglycemic rats were capable of endogenous insulin secretion, which was enhanced significantly versus controls 12 h after burn injury. DNA binding data of liver nuclear extracts showed a robust and significant activation of the noncanonical NF-κB pathway in the hyperglycemic versus control burn animals, including increased NF-κB-inducing kinase expression (p < 0.05). Liver acute-phase proteins and cytokine expression were increased, whereas secretion of constitutive proteins was decreased after burn injury in hyperglycemic versus control animals (p < 0.05). These results indicate that burn injury to the skin rapidly activated canonical and noncanonical NF-κB pathways in the liver. Robust activation of the NF-κB noncanonical pathway was associated with increased expression of inflammatory markers and acute-phase proteins, and impaired glucose metabolism. Hyperglycemia is detrimental to burn outcome by augmenting inflammation mediated by hepatic noncanonical NF-κB pathway activation.

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Gene Expression and Cytokine and Enzyme Activation in the Liver After a Burn Injury

Cited by 21 publications

References 0 publications

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

Melatonin Protection against Burn-Induced Hepatic Injury by Down-Regulation and Nuclear Factor Kappa B Activation

Hyperglycemia Exacerbates Burn-Induced Liver Inflammation via Noncanonical Nuclear Factor-κB Pathway Activation

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