Systemic inflammation and remote organ injury following trauma require HMGB1

Levy, Ryan M.; Mollen, Kevin P.; Prince, José M.; Kaczorowski, David J.; Vallabhaneni, Raghuveer; Liu, Shiguang; Tracey, Kevin J.; Lotze, Michael T.; Hackam, David J.; Fink, Mitchell P.; Vodovotz, Yoram; Billiar, Timothy R.

doi:10.1152/ajpregu.00272.2007

Cited by 210 publications

(165 citation statements)

References 51 publications

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“…It was found that an HMGB1 neutralizing antibody protects WT mice (C3H/HeouJ) but not TLR4-defective (C3H/HEJ) mice from liver ischemia reperfusion injury (39). Since then, several studies have demonstrated a role for HMGB1-TLR4 interactions in the pathology of diseases including inflammation-induced seizures (40), inflammation-induced skin cancer (41), end organ injury following tissue trauma (42), and ischemic kidney injury (43).…”

Section: Discussionmentioning

confidence: 99%

High Mobility Group Box 1 Inhibits Human Pulmonary Artery Endothelial Cell Migration via a Toll-like Receptor 4- and Interferon Response Factor 3-dependent Mechanism(s)

Bauer

Shapiro

Billiar

et al. 2013

Journal of Biological Chemistry

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Background: TLR4 contributes to pulmonary hypertension, a disease of endothelial dysfunction. The role of HMGB1, one endogenous ligand of TLR4, remains unexplored. Results: HMGB1 inhibited pulmonary artery endothelial cell migration, which was reversed by TLR4 or IRF3 siRNA. Conclusion: HMGB1 inhibits pulmonary artery endothelial cell migration via TLR4-and IRF3-dependent mechanism(s). Significance: HMGB1, via TLR4, inhibits a critical process for pulmonary vascular regeneration.

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Section: Discussionmentioning

confidence: 99%

High Mobility Group Box 1 Inhibits Human Pulmonary Artery Endothelial Cell Migration via a Toll-like Receptor 4- and Interferon Response Factor 3-dependent Mechanism(s)

Bauer

Shapiro

Billiar

et al. 2013

Journal of Biological Chemistry

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“…TNF-α also participates in the generation of free radicals such as NO [110,121]. Clinical studies have demonstrated that levels of several inflammatory mediators, such as IL-6, IL-8 and IL-10, correlate closely with severity of injury and complication rates [101][102][103][104]. From the family of DAMPs, serum HMGB1 was significantly increased in patients with sepsis, and the highest concentrations were observed in samples from patients who died [106].…”

Section: Human Studies Of T/hsmentioning

confidence: 99%

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Namas¹,

Ghuma²,

Hermus

et al. 2008

Libyan Journal of Medicine

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Abstract; Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

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“…4 Similarly, HMGB1 appears to regulate early inflammatory signaling in both hemorrhagic shock 9 and peripheral tissue injury. 10 Cisplatin was the first identified member of the platinating group of chemotherapeutics. It has been used clinically for more than 30 years in the treatment of numerous cancers.…”

mentioning

confidence: 99%

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury†

et al. 2009

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The nuclear protein high mobility group box 1 (HMGB1) is an important inflammatory mediator involved in the pathogenesis of liver ischemia/reperfusion (I/R) injury. Strategies aimed at preventing its release from stressed or damaged cells may be beneficial in preventing inflammation after I/R. Cisplatin is a member of the platinating chemotherapeutic agents and can induce DNA lesions that are capable of retaining high mobility group proteins inside the nucleus of cells. In vitro studies in primary cultured rat hepatocytes show that nontoxic concentrations of cisplatin can sequester HMGB1 inside the nucleus of hypoxic cells. Similarly, the in vivo administration of nontoxic doses of cisplatin prevents liver damage associated with a well-established murine model of hepatic I/R as measured by lower circulating serum aminotransferase levels, lower hepatic inflammatory cytokine levels including tumor necrosis factor ␣ and interleukin-6, lower inducible NO synthase expression, and fewer I/R-associated histopathologic changes. The mechanism of action in vivo appears to involve the capacity of cisplatin to prevent the I/R-induced release of HMGB1 as well as to alter cell survival and stress signaling in the form of autophagy and mitogen-activated protein kinase activation, respectively. Conclusion: Low, nontoxic doses of cisplatin can sequester HMGB1 inside the nucleus of redox-stressed hepatocytes in vitro and prevent its release in vivo in a murine model of hepatic I/R. Furthermore, cell survival and stress signaling pathways are altered by low-dose cisplatin. Therefore, platinating agents may provide a novel approach to mitigating the deleterious effects of I/R-mediated disease processes. (HEPATOLOGY 2009;50:565-574.)

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Systemic inflammation and remote organ injury following trauma require HMGB1

Cited by 210 publications

References 51 publications

High Mobility Group Box 1 Inhibits Human Pulmonary Artery Endothelial Cell Migration via a Toll-like Receptor 4- and Interferon Response Factor 3-dependent Mechanism(s)

High Mobility Group Box 1 Inhibits Human Pulmonary Artery Endothelial Cell Migration via a Toll-like Receptor 4- and Interferon Response Factor 3-dependent Mechanism(s)

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury†

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