Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review

Lü, Ben; Wang, Ce; Mao, Wang; Li, Wei; Chen, Fangping; Tracey, Kevin J.; Wang, Haichao

doi:10.1586/1744666x.2014.909730

Cited by 127 publications

(113 citation statements)

References 169 publications

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“…Considering the nuclear origin of HMGB1, one might expect that the release of this protein follows similar kinetics as nucleosomes and DNA. Of note, however, HMGB1 can also be secreted actively (28); this, together with the possibility that nucleosomes, DNA and HMGB1 measured in BALF may at is consistent with the fact that the release of mature IL-1β requires activation of caspase-1 mediated by inflammasomes.…”

Section: Tlr9 Deficiency Is Associated With Strongly Increased Lung Csupporting

confidence: 66%

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Meer

Achouiti

Ende

et al. 2016

Mol Med

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Section: Tlr9 Deficiency Is Associated With Strongly Increased Lung Csupporting

confidence: 66%

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Meer

Achouiti

Ende

et al. 2016

Mol Med

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“…At sites of intestinal inflammation, dying cells release pro-inflammatory molecules such as HMGB1 which is an endogenous ligand for TLR4 (33–36), and which has been linked to the development of lung injury in other settings but not in the setting of neonatal inflammation (26, 37, 38). As shown in Figure 3A, NEC in human infants and in wild-type mice was associated with significant HMGB1 release into the systemic circulation, consistent with prior reports linking HMGB1 expression with NEC in mice(39, 40).…”

Section: Resultsmentioning

confidence: 99%

Pulmonary Epithelial TLR4 Activation Leads to Lung Injury in Neonatal Necrotizing Enterocolitis

Jia

Sodhi

Yamaguchi

et al. 2016

The Journal of Immunology

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We seek to define the mechanisms leading to the development of lung disease in the setting of neonatal necrotizing enterocolitis (NEC), a life-threatening gastrointestinal disease of premature infants characterized by the sudden onset of intestinal necrosis. NEC development in mice requires activation of the lipopolysaccharide receptor toll-like receptor-4 (TLR4) on the intestinal epithelium, through its effects on modulating epithelial injury and repair. Although NEC-associated lung injury is more severe than the lung injury that occurs in premature infants without NEC, the mechanisms leading to its development remain unknown. We now show that the TLR4 expression in the lung gradually increases during postnatal development, and that mice and humans with NEC-associated lung inflammation express higher levels of pulmonary TLR4 than age-matched controls. NEC in wild-type newborn mice resulted in significant pulmonary injury that was prevented by deletion of TLR4 from the pulmonary epithelium, indicating a role for pulmonary TLR4 in lung injury development. Mechanistically, intestinal epithelial TLR4 activation induced high mobility group box-1 (HMGB1) release from the intestine which activated pulmonary epithelial TLR4, leading to the induction of the neutrophil recruiting C-X-C motif chemokine-5 (CXCL5) and the influx of pro-inflammatory neutrophils to the lung. Strikingly, the aerosolized administration of a novel carbohydrate TLR4 inhibitor prevented CXCL5 upregulation and blocked NEC-induced lung injury in mice. These findings illustrate the critical role of pulmonary TLR4 in the development of NEC-associated lung injury, and suggest that inhibition of this innate immune receptor in the neonatal lung may prevent this devastating complication of NEC.

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“…Another DAMP protein HMGB1 has also been shown to be an early mediator of sterile inflammation (33, 34). Inhibition of HMGB1 activity with neutralizing antibody was also shown to significantly decrease liver damage after I/R, whereas administration of recombinant HMGB1 was shown to worsen I/R injury (35).…”

Section: Discussionmentioning

confidence: 99%

Blocking Cold-Inducible RNA-Binding Protein Protects Liver From Ischemia-Reperfusion Injury

Godwin

Yang

Sharma

et al. 2015

Shock

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Cold inducible RNA-binding protein (CIRP) is a nuclear protein which has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. Blood and liver tissues were collected 24 h after I/R for various measurements and a 10-day survival study was performed. CIRP released into the circulation was significantly increased 24 h after hepatic I/R. Anti-CIRP antibody treatment markedly reduced hepatocellular damage markers and significantly improved the liver microarchitecture. Anti-CIRP also reduced the systemic and local inflammation demonstrated by attenuation in both serum and hepatic levels of interleukin 6. The expression of neutrophil-attracting chemokine as well as liver neutrophil infiltration was reduced by anti-CIRP treatment. Anti-CIRP also dramatically decreased the amount of apoptosis and nitrosative stress, evidenced by decrease in TUNEL staining and inducible nitric oxide synthase and cyclooxygenase-2 levels, respectively. Finally, the 10-day survival rate was increased from 37.5% in the vehicle group to 75% in the anti-CIRP treatment group. Thus, targeting CIRP offers potential therapeutic implications in the treatment of hepatic I/R injury.

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Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review

Cited by 127 publications

References 169 publications

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Pulmonary Epithelial TLR4 Activation Leads to Lung Injury in Neonatal Necrotizing Enterocolitis

Blocking Cold-Inducible RNA-Binding Protein Protects Liver From Ischemia-Reperfusion Injury

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