Plasma Concentrations of High-Mobility Group Box Protein 1, Soluble Receptor for Advanced Glycation End-Products and Circulating DNA in Patients with Acute Pancreatitis

Kocsis, Ágnes Katalin; Szabolcs, Annamária; Höfner, P.; Takács, Tamás; Farkas, Gyula; Boda, Krisztina; Mándi, Yvette

doi:10.1159/000181172

Cited by 57 publications

(50 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pancreatic acinar cell necrosis is an early event in AP, and serum HMGB1 levels are significantly elevated in patients with AP. Furthermore, high HMGB1 serum levels correlate with worsening clinical course and mortality (32). Similar results have been observed in preclinical animal models of AP (33).…”

Section: Discussionsupporting

confidence: 78%

Carbon monoxide–based therapy ameliorates acute pancreatitis via TLR4 inhibition

Xue¹,

Habtezion²

2013

J. Clin. Invest.

View full text Add to dashboard Cite

The protective role of hemeoxygenase-1 (HO-1) in various inflammatory conditions is mediated in part by its products, carbon monoxide (CO) and biliverdin. Here we investigated a therapeutic role for CO and COprimed cells in acute pancreatitis (AP). In a mouse model of AP, treatment with CO-releasing molecule-2 (CORM-2) decreased mortality, pancreatic damage, and lung injury. CORM-2 decreased systemic inflammatory cytokines, suppressed systemic and pancreatic macrophage TNF-α secretion, and inhibited macrophage TLR4 receptor complex expression. In both human and mouse cells, CORM-2 inhibited endogenous and exogenous ligand-dependent TLR4 activation, which indicates that CORM-2 could be therapeutic for both early and late stages of AP, which involve sterile-and endotoxin-mediated inflammation, respectively. Mice engrafted with TLR4-deficient hematopoietic cells were protected against caerulein-induced AP. In the absence of leukocyte TLR4 expression, CORM-2 did not confer additional protection, which indicates that CORM-2-dependent effects are mediated via suppression of macrophage TLR4 activation. We determined that CO was directly responsible for the protective effects of CORM-2 in AP, as inactive forms of CORM-2 were ineffective. Importantly, adoptive transfer of CORM-2-primed cells reduced AP. Such a therapeutic approach would translate the beneficial effects of CO-based therapies, avoiding CO-or CO-RM-mediated toxicities in AP and a wide range of diseases.

show abstract

Section: Discussionsupporting

confidence: 78%

Carbon monoxide–based therapy ameliorates acute pancreatitis via TLR4 inhibition

Xue¹,

Habtezion²

2013

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…In this study, we have generated acute pancreatitis models with 3 distinguishable levels of severities, with which we have established the association of levels in circulating histones with severity scores, particularly of necrotic scores of pancreas in pathological examination. In human acute pancreatitis, nuclear breakdown products, such as HMGB1 28,29 and DNA, 30,31 have already been shown to be released into the circulation and correlated with disease severity. Treatment with anti-H3 antibody suppresses serum HMGB1 levels and improves survival of L-arginine-induced acute pancreatitis in mice.…”

Section: Discussionmentioning

confidence: 99%

Circulating Histone Levels Reflect Disease Severity in Animal Models of Acute Pancreatitis

Ou¹,

Cheng²,

Liu³

et al. 2015

Pancreas

View full text Add to dashboard Cite

show abstract

“…Monitoring levels of circulating DNA has been proposed as a useful tool in the noninvasive diagnosis of human diseases. Serum DNA level is elevated significantly in patients with severe AP and may be an early predictor of severity in AP (134)(135)(136)(137). Apoptotic or necrotic cells are the primary source of circulating DNA during AP.…”

Section: Dna and Acute Pancreatitismentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

128

View full text Add to dashboard Cite

The pancreas is a dual-purpose gland with exocrine and endocrine functions. The exocrine pancreas produces digestive proteases in inactive proenzyme form, namely zymogens. The pancreas is normally able to protect itself from zymogen activation by synthesis of protease inhibitors such as pancreatic secretory trypsin inhibitor and serine protease inhibitor (for example, SPINK1/Spink3). By contrast, pancreatic autodigestion and subsequent AP is initiated once these defenses are impaired. In studies of rodent models (for example, repetitive cerulein or L-arginine injections, choline-deficient ethionine supplementation [CDE] diet, perfusion of taurocholate into the biliary or pancreatic duct and surgical ligation or infusion of pancreatic duct models), some essential pathogenic AP events have been identified (see Figure 1) (15,16).The development of AP involves a complex cascade of events (17), which start with injury or disruption of the pan- Cell Death and DAMPs in Acute PancreatitisRui Kang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, and Daolin Tang Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP . Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP . DAMPs might be an attractive therapeutic target in AP.

show abstract

Plasma Concentrations of High-Mobility Group Box Protein 1, Soluble Receptor for Advanced Glycation End-Products and Circulating DNA in Patients with Acute Pancreatitis

Cited by 57 publications

References 31 publications

Carbon monoxide–based therapy ameliorates acute pancreatitis via TLR4 inhibition

Carbon monoxide–based therapy ameliorates acute pancreatitis via TLR4 inhibition

Circulating Histone Levels Reflect Disease Severity in Animal Models of Acute Pancreatitis

Cell Death and DAMPs in Acute Pancreatitis

Contact Info

Product

Resources

About