HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice

Sappington, Penny L.; Yang, Runkuan; Yang, Huan; Tracey, Kevin J.; Delude, Russell L.; Fink, Mitchell P.

doi:10.1053/gast.2002.35391

Cited by 293 publications

(249 citation statements)

References 38 publications

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“…Exposure of epithelial cell monolayers to HMGB-1 caused the monolayers to become "leaky," so that large, normally excluded molecules passed through the cell layer. Epithelial leakage mediated by HMGB-1 was not attributable to toxicity, but required signaling through MAP kinases, NF-B, and nitric oxide (22). This finding reveals a potentially important mechanism of HMGB-1 toxicity.…”

Section: Proinflammatory Activities Of Hmgb-1mentioning

confidence: 75%

“…An important pathobiologic activity of HMGB-1 was recently revealed in studies performed by Sappington and colleagues, which implicated HMGB-1 as a mediator of epithelial barrier dysfunction (22). Exposure of epithelial cell monolayers to HMGB-1 caused the monolayers to become "leaky," so that large, normally excluded molecules passed through the cell layer.…”

Section: Proinflammatory Activities Of Hmgb-1mentioning

confidence: 99%

See 1 more Smart Citation

High mobility group box chromosomal protein 1 as a nuclear protein, cytokine, and potential therapeutic target in arthritis

Ulloa¹,

Batliwalla²,

Andersson³

et al. 2003

Arthritis & Rheumatism

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Section: Proinflammatory Activities Of Hmgb-1mentioning

confidence: 75%

Section: Proinflammatory Activities Of Hmgb-1mentioning

confidence: 99%

High mobility group box chromosomal protein 1 as a nuclear protein, cytokine, and potential therapeutic target in arthritis

Ulloa¹,

Batliwalla²,

Andersson³

et al. 2003

Arthritis & Rheumatism

Self Cite

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“…No longer an innocent bystander, the epithelial-lined mucosa at each of these sites has been shown to possess all of the required armamentarium to allow an effective response to invading challenges, and to lead the battle to neutralize potential microbial threats (14)(15)(16). Not only is the epithelium able to respond to potentially dangerous microbial products, it also may sense endogenous molecules that are released during conditions of stress, hypoxia, or injury-so-called danger molecules that may play a critical role in the development of mucosal inflammation (17)(18)(19). In order, therefore, to understand the pathogenesis of mucosal inflammation and to assist in the rational design of anti-inflammatory strategies, it is necessary to define the receptors and signaling pathways that mediate the inflammatory response with respect to the epithelium itself.…”

Section: The Clinical and Scientific Importance Of Mucosal Inflammationmentioning

confidence: 99%

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

Gribar

Richardson

Sodhi

et al. 2008

Mol Med

142

109

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Diseases of mucosal inflammation represent important causes of morbidity and mortality, and have led to intense research efforts to understand the factors that lead to their development. It is well accepted that a breakdown of the normally impermeant epithelial barrier of the intestine, the lung, and the kidney is associated with the development of inflammatory disease in these organs, yet significant controversy exists as to how this breakdown actually occurs, and how such a breakdown may lead to inflammation. In this regard, much work has focused upon the role of the epithelium as an "innocent bystander," a target of a leukocyte-mediated inflammatory cascade that leads to its destruction in the mucosal inflammatory process. However, recent evidence from a variety of laboratories indicates that the epithelium is not merely a passive component in the steps that lead to mucosal inflammation, but is a central participant in the process. In addressing this controversy, we and others have determined that epithelial cells express Toll-like receptors (TLRs) of the innate immune system, and that activation of TLRs by endogenous and exogenous ligands may play a central role in determining the balance between a state of "mucosal homeostasis," as is required for optimal organ function, and "mucosal injury," leading to mucosal inflammation and barrier breakdown. In particular, activation of TLRs within intestinal epithelial cells leads to the development of cellular injury and impairment in mucosal repair in the pathogenesis of intestinal inflammation, while activation of TLRs in the lung and kidney may participate in the development of pneumonitis and nephritis respectively. Recent work in support of these concepts is extensively reviewed, while essential areas of further study that are required to determine the significance of epithelial TLR signaling during states of health and disease are outlined.

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“…These data, along with results from our laboratory showing that exposure to HMGB1 increases the permeability of Caco-2 enterocyte-like monolayers in vitro (30), prompted to us to measure circulating HMGB1 levels in a cohort of adult trauma patients with physiological and/or biochemical evidence of hemorrhagic shock. Because serum HMGB1 concentrations were significantly elevated in patients with trauma-induced hemorrhagic shock, we sought to determine whether HMGB1 contributes to the development of gut barrier dysfunction in a well-characterized murine model of HS/R.…”

Section: Introductionmentioning

confidence: 99%

Anti-HMGB1 Neutralizing Antibody Ameliorates Gut Barrier Dysfunction and Improves Survival after Hemorrhagic Shock

Yang

Harada

Mollen

et al. 2006

Mol Med

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207

156

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Intestinal barrier dysfunction occurs following hemorrhagic shock and resuscitation (HS/R). High-mobility group B1 (HMGB1) has been shown to increase the permeability of Caco-2 human enterocyte-like epithelial monolayers in vitro. In this study, we found that serum concentrations of HMGB1 were higher in blood samples obtained from 25 trauma victims with hemorrhagic shock than in 9 normal volunteers. We also studied whether treatment with anti-HMGB1 antibody can ameliorate HS/R-induced gut barrier dysfunction in mice. Animals were shocked by withdrawal of blood to maintain mean arterial pressure at 25 to 30 mmHg for 2 h. After resuscitation with shed blood plus Ringer's lactate solution, the mice were treated with either anti-HMGB1 antibody or nonimmune rabbit IgG. Serum HMGB1 concentrations were significantly higher in trauma victims than control mice. Treatment with anti-HMGB1 antibody improved survival at 24 h and ameliorated the development of ileal mucosal hyperpermeability to FITC-labeled dextran. At 24 h after HS/R, treatment with anti-HMGB1 antibody decreased bacterial translocation to mesenteric lymph nodes and was associated with lower circulating concentrations of IL-6 and IL-10. These data support the notion that HMGB1 is a mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1 antibodies warrant further evaluation as a therapeutic to ameliorate the morbidity of HS/R in trauma patients.

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HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice

Cited by 293 publications

References 38 publications

High mobility group box chromosomal protein 1 as a nuclear protein, cytokine, and potential therapeutic target in arthritis

High mobility group box chromosomal protein 1 as a nuclear protein, cytokine, and potential therapeutic target in arthritis

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

Anti-HMGB1 Neutralizing Antibody Ameliorates Gut Barrier Dysfunction and Improves Survival after Hemorrhagic Shock

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