Fecal HMGB1 Is a Novel Marker of Intestinal Mucosal Inflammation in Pediatric Inflammatory Bowel Disease

Vitali, Roberta; Stronati, Laura; Negroni, Anna; Nardo, Giovanni Di; Pierdomenico, Maria; Giudice, Emanuela Del; Rossi, Paolo; Cucchiara, Salvatore

doi:10.1038/ajg.2011.231

Cited by 105 publications

(85 citation statements)

References 42 publications

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“…Furthermore, HMGB1 antagonism using anti-HMGB1 antibody or ethyl pyruvate ameliorates colitis in the DSS and Il10 -/-mouse models, respectively (7,8). Very little is known about HMGB1 in human IBD, just that children with IBD have increased levels of this protein in their feces (9). These data reflect the fact that the majority of HMGB1 research has focused on its extracellular functions during inflammation, despite it being concurrently found in the cell cytosol under these conditions.…”

Section: Introductionmentioning

confidence: 99%

Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation

Zhu¹,

Messer²,

Wang³

et al. 2015

J. Clin. Invest.

172

134

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Section: Introductionmentioning

confidence: 99%

Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation

Zhu¹,

Messer²,

Wang³

et al. 2015

J. Clin. Invest.

172

134

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“…Administration of neutralizing antibody against HMGB1 or blockade by soluble RAGE was also shown to be effective in various organ injuries such as acute lung injury, ischemia-reperfusion hepatic injury or rheumatoid arthritis [33,34,35]. Recently, it was shown that HMGB1 is secreted by human inflamed intestinal tissues and is abundantly found in the stool of patients with IBD [36]. It was also shown that HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice [37].…”

Section: Discussionmentioning

confidence: 99%

Recombinant Thrombomodulin Modulates Murine Colitis Possibly via High-Mobility Group Box 1 Protein Inhibition

Ueda¹,

Higashiyama²,

Narimatsu³

et al. 2015

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Background and Aim: Thrombomodulin (TM) is an anticoagulant cofactor protein. We hypothesized that its recombinant soluble TM (rhTM) form, widely used to treat disseminated intravascular coagulation, might have anti-inflammatory action in inflammatory bowel disease (IBD), possibly through its inhibition of high-mobility group box 1 protein (HMGB1). Methods: We investigated inflammatory effects of HMGB1 and anti-inflammatory effect of rhTM in dextran sulfate sodium (DSS)-treated mice, some cell lines and ulcerative colitis (UC) patients, particularly focusing on changes of vascular endothelial adhesion molecules. Results: Treatments with rhTM significantly attenuated DSS-treated mice clinically and histologically. The mRNA levels of proinflammatory cytokines and adhesion molecules were decreased by rhTM. Increased inflammatory cells in the colonic mucosa strongly expressed HMGB1 in the cytoplasm in the DSS-treated mice and UC patients' colonic mucosa, which were significantly decreased by rhTM in mice. In in vitro experiments, rhTM significantly decreased the mRNA levels of tumor necrosis factor-alpha (TNF-α) and adhesion molecules increased by endotoxin exposures in RAW 264.7 (macrophage cell line) and bEND.3 cells (endothelial cell line), suggesting the proinflammatory role of HMGB1 in TNF-α production from macrophages. Conclusions: These findings suggest that rhTM may be useful for the treatment of IBD by attenuating inflammatory cytokine production and adhesion molecule expression, partly because of its inhibition of HMGB1.

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“…However, cytoplasmic HMGB1 levels increased significantly in inflamed tissue. Because HMGB1 is constitutively expressed in the nuclei of almost all eukaryotic cells and transfers to the cytoplasm during inflammation, the authors considered increased fecal HMGB1 to come from active secretion of protein stored in the nucleus rather than ''de novo'' synthesis [47]. However, it was not determined whether HMGB1 nuclear-cytoplasmic transfer would affect its normal intra-nuclear function.…”

Section: Hmgb1 and Ibd Expression Of Hmgb1 In Ibdmentioning

confidence: 99%

“…Similarly, HMGB1 is abundantly present in the feces of pediatric IBD patients [47]. The amount of fecal HMGB1 correlated with mucosal inflammation (even subclinical) and healing, indicating the potential usefulness for HMGB1 in monitoring disease progression and assessing therapeutic outcomes in IBD patients [48].…”

Section: Hmgb1 and Ibd Expression Of Hmgb1 In Ibdmentioning

confidence: 99%

Role of high-mobility group box 1 protein in inflammatory bowel disease

Wang

Gong

et al. 2015

Inflamm. Res.

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High-mobility group box 1 (HMGB1) protein is a nuclear non-histone DNA-binding protein. It is released into the extracellular milieu and mediates inflammatory responses, which contribute to the pathogenesis of numerous inflammatory diseases, including inflammatory bowel disease (IBD). An online search was performed in PubMed and Web of Science databases for articles providing evidence on the role of HMGB1 in IBD. HMGB1 plays an important role in IBD pathogenesis. Application of HMGB1 antagonists reduced inflammatory reactions and ameliorated colitis in rodent models, which may provide new insights into the diagnosis and treatment of IBD.

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Fecal HMGB1 Is a Novel Marker of Intestinal Mucosal Inflammation in Pediatric Inflammatory Bowel Disease

Cited by 105 publications

References 42 publications

Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation

Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation

Recombinant Thrombomodulin Modulates Murine Colitis Possibly via High-Mobility Group Box 1 Protein Inhibition

Role of high-mobility group box 1 protein in inflammatory bowel disease

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