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

Hu, Zhen; Wang, Xiaoyun; Gong, Lei; Wu, Guangyong; Peng, Xiaobin; Tang, Xuejun

doi:10.1007/s00011-015-0841-x

Cited by 25 publications

(20 citation statements)

References 66 publications

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“…Across all clusters, the most sensitive parameters are cancer proliferation and death rates directly present in the cancer Equation (13). From the third column in Figure 4A, we conclude that for all clusters, increased cancer proliferation coefficients correspond to faster convergence to the steady-state, while increased cancer death rates lead to a slower convergence.…”

Section: Sensitivity Analysismentioning

confidence: 89%

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Data Driven Mathematical Model of Colon Cancer Progression

Kirshtein

Akbarinejad

Hao

et al. 2020

JCM

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Every colon cancer has its own unique characteristics, and therefore may respond differently to identical treatments. Here, we develop a data driven mathematical model for the interaction network of key components of immune microenvironment in colon cancer. We estimate the relative abundance of each immune cell from gene expression profiles of tumors, and group patients based on their immune patterns. Then we compare the tumor sensitivity and progression in each of these groups of patients, and observe differences in the patterns of tumor growth between the groups. For instance, in tumors with a smaller density of naive macrophages than activated macrophages, a higher activation rate of macrophages leads to an increase in cancer cell density, demonstrating a negative effect of macrophages. Other tumors however, exhibit an opposite trend, showing a positive effect of macrophages in controlling tumor size. Although the results indicate that for all patients the size of the tumor is sensitive to the parameters related to macrophages, such as their activation and death rate, this research demonstrates that no single biomarker could predict the dynamics of tumors.

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Section: Sensitivity Analysismentioning

confidence: 89%

“…In particular, HMGB1 activates dendritic cells (DCs) [12]. There is evidence that the expressions of HMGB1 and RAGE, its receptor, are significantly higher in ulcerative colitis than in control cases [13]. HMGB1 has been observed in other cancers, as a result of treatments by radiotherapy and chemotherapy [12,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Data Driven Mathematical Model of Colon Cancer Progression

Kirshtein

Akbarinejad

Hao

et al. 2020

JCM

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“…HMGB1 is known for its proinflamamtory role in the intestine and other tissues including liver [10] , [31] , [32] . High circulatory levels of HMGB1 was associated with increased expression of proinflammatory mediators IL1β, MCP1, TGF-β and IFN-γ [11] , [33] .…”

Section: Discussionmentioning

confidence: 99%

HMGB1-RAGE pathway drives peroxynitrite signaling-induced IBD-like inflammation in murine nonalcoholic fatty liver disease

et al. 2017

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Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD)-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD) yet the mechanisms remain unknown. The present study identifies high mobility group box 1 (HMGB1) as a key mediator of intestinal inflammation in NAFLD and outlines a detailed redox signaling mechanism for such a pathway. NAFLD mice showed liver damage and release of elevated HMGB1 in systemic circulation and increased intestinal tyrosine nitration that was dependent on NADPH oxidase. Intestines from NAFLD mice showed higher Toll like receptor 4 (TLR4) activation and proinflammatory cytokine release, an outcome strongly dependent on the existence of NAFLD pathology and NADPH oxidase. Mechanistically intestinal epithelial cells showed the HMGB1 activation of TLR-4 was both NADPH oxidase and peroxynitrite dependent with the latter being formed by the activation of NADPH oxidase. Proinflammatory cytokine production was significantly blocked by the specific peroxynitrite scavenger phenyl boronic acid (FBA), AKT inhibition and NADPH oxidase inhibitor Apocynin suggesting NADPH oxidase-dependent peroxynitrite is a key mediator in TLR-4 activation and cytokine release via an AKT dependent pathway. Studies to ascertain the mechanism of HMGB1-mediated NADPH oxidase activation showed a distinct role of Receptor for advanced glycation end products (RAGE) as the use of inhibitors targeted against RAGE or use of deformed HMGB1 protein prevented NADPH oxidase activation, peroxynitrite formation, TLR4 activation and finally cytokine release. Thus, in conclusion the present study identifies a novel role of HMGB1 mediated inflammatory pathway that is RAGE and redox signaling dependent and helps promote ectopic intestinal inflammation in NAFLD.

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“…Silencing of TLR2 or TLR4 increases overall HDAC activity and considerably mitigates the effects of phenyl butyrate on host defense peptide expression (29). Interestingly, TLR2 and TLR4 are two of the main receptors for recognizing extracellular highmobility group box 1 (HMGB1), which plays an important role in the pathogenesis of IBD and whose secretion is also controlled by HDAC activity (31,32). HMGB1 is typically localized in the nucleus but can be released into the extracellular space upon stress or tissue damage acting as a damage-associated molecular pattern (DAMP) that induces pro-inflammatory responses by binding its receptors (33).…”

Section: Pan-hdac Inhibitionmentioning

confidence: 99%

Histone Deacetylases in the Inflamed Intestinal Epithelium—Promises of New Therapeutic Strategies

Gerbeth

Glauben

2021

Front. Med.

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The intestinal epithelium is a complex, dynamic barrier that separates luminal contents from the immune compartment while mediating nutrient absorption and controlled passage of antigens to convey oral tolerance. A compromised epithelial barrier often leads to inflammation because immune cells in the lamina propria come into direct contact with luminal antigens. Defects in epithelial cell function were also shown to be involved in the etiology of inflammatory bowel diseases. These are severe, chronically relapsing inflammatory conditions of the gastrointestinal tract that also increase the risk of developing colorectal cancer. Despite major efforts of the scientific community, the precise causes and drivers of these conditions still remain largely obscured impeding the development of a permanent cure. Current therapeutic approaches mostly focus on alleviating symptoms by targeting immune cell signaling. The protein family of histone deacetylases (HDACs) has gained increasing attention over the last years, as HDAC inhibitors were shown to be potent tumor cell suppressors and also alleviate morbid inflammatory responses. Recent research continuously identifies new roles for specific HDACs suggesting that HDACs influence the cell signaling network from many different angles. This makes HDACs very interesting targets for therapeutic approaches but predicting effects after system manipulations can be difficult. In this review, we want to provide a comprehensive overview of current knowledge about the individual roles of HDACs in the intestinal epithelium to evaluate their therapeutic potential for inflammatory conditions of the gut.

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

Cited by 25 publications

References 66 publications

Data Driven Mathematical Model of Colon Cancer Progression

Data Driven Mathematical Model of Colon Cancer Progression

HMGB1-RAGE pathway drives peroxynitrite signaling-induced IBD-like inflammation in murine nonalcoholic fatty liver disease

Histone Deacetylases in the Inflamed Intestinal Epithelium—Promises of New Therapeutic Strategies

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