Dengue fatal cases present virus-specific HMGB1 response in peripheral organs

Oliveira, Edson R. A.; Póvoa, Tiago F.; Nuovo, Gerard J.; Allonso, Diego; Salomão, Natália Gedeão; Basílio-de-Oliveira, Carlos Alberto; Geraldo, Luiz Henrique Medeiros; Fonseca, Celina G.; Lima, Flávia Regina Souza; Mohana‐Borges, Ronaldo; Paes, Marciano Viana

doi:10.1038/s41598-017-16197-5

Cited by 24 publications

(20 citation statements)

References 74 publications

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“…TLR4 signaling has been reported to contribute to tissue damage in both pathogenic hepatic injury and sterile inflammatory hepatitis [31][32][33]. As a ligand of TLR4, HMGB1 plays an important role in many viral infection models [34][35][36]. Therefore, we examined whether TLR4 signaling is also critical in a MHV infection model.…”

Section: Mhv Infection Mediates Hepatic Injury Through a Tlr4-dependementioning

confidence: 99%

Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway

Shi¹,

Yu²,

Zhang³

et al. 2020

International Immunopharmacology

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Various human disorders are cured by the use of licorice, a key ingredient of herbal remedies. Glycyrrhizic acid (GL), a triterpenoid glycoside, is the aqueous extract from licorice root. Glycyrrhetinic acid (GA) has been reported to be a major bioactive hydrolysis product of GL and has been regarded as an anti-inflammatory agent for the treatment of a variety of inflammatory diseases, including hepatitis. However, the mechanism by which GA inhibits viral hepatic inflammatory injury is not completely understood. In this study, we found that, by consecutively treating mice with a traditional herbal recipe, licorice plays an important role in the detoxification of mice. We also employed a murine hepatitis virus (MHV) infection model to illustrate that GA treatment inhibited activation of hepatic inflammatory responses by blocking high-mobility group box 1 (HMGB1) cytokine activity. Furthermore, decreased HMGB1 levels and downstream signaling triggered by injection of a neutralizing HMGB1 antibody or TLR4 gene deficiency, also significantly protected against MHV-induced severe hepatic injury. Thus, our findings characterize GA as a hepatoprotective therapy agent in hepatic infectious disease not only by suppressing HMGB1 release and blocking HMGB1 cytokine activity, but also via an underlying viral-induced HMGB1-TLR4 immunological regulation axis that occurs during the cytokine storm. The present study provides a new therapy strategy for the treatment of acute viral hepatitis in the clinical setting.

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Section: Mhv Infection Mediates Hepatic Injury Through a Tlr4-dependementioning

confidence: 99%

Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway

Shi¹,

Yu²,

Zhang³

et al. 2020

International Immunopharmacology

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“…The level of peripheral mononuclear cell apoptosis around defervescence also well correlated with SD in children [ 23 ]. In addition, high mobility group box 1 (HMGB1) [ 38 ], TGF-beta [ 39 ], TNF-alpha, nitric oxide and NS1 [ 4 , 40 ] related to apoptosis were reported at increased levels in SD patients’ samples, further supporting the role of apoptosis in SD and cfDNA as its proxy indicator. Undoubtedly, the knowledge on the source of this cfDNA would aid in the further understanding of pathogenesis too.…”

Section: Discussionmentioning

confidence: 99%

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue

Phuong

Manh

Dumre

et al. 2019

Ann Clin Microbiol Antimicrob

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BackgroundConsiderable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators, among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase.MethodsThis was a hospital-based prospective cohort study conducted in Vietnam. All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters (including progression to SD) until discharged. Plasma samples collected during acute phase (6–48 h before defervescence) were used to estimate the level of cfDNA.ResultsOf the 61 dengue patients, SD patients (n = 8) developed shock syndrome in 4.8 days (95% CI 3.7–5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55–0.88; p = 0.0493).ConclusionsTaken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD.Electronic supplementary materialThe online version of this article (10.1186/s12941-019-0309-x) contains supplementary material, which is available to authorized users.

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“…Previous studies have reported the roles of HMGB-1 and ICAM-1 in dengue virus infection where both proteins were released by dengue infected endothelium or immune cells [39,53] and increased permeability of endothelial cells leading to vascular leakage [54,55]. They were detected at a higher concentration in dengue patients [56,57], while HMGB-1 was also detected in the peripheral organs of dengue fatal cases [38], which further justified the role of HMGB-1 and ICAM-1 in the progression of severe dengue.…”

Section: Plos Onementioning

confidence: 97%

“…The level of 14 commonly studied cytokines, chemokines, adhesion molecules and growth factors (CCL2, CCL5, CCL20, CD25, CXCL1, CXCL6, CXCL9, CXCL10, CXCL11, IL-18, TNF-a, VEGF-A, HMGB-1 and ICAM-1) in the 40 selected serum samples were assessed using the Human Magnetic Luminex multiplex screening assay based on flow cytometric analysis of magnetic antibody-coated microbeads targeting the analytes of interest (R&D Systems, Minneapolis, MN, USA). These 14 cytokines have been shown to have a role during dengue virus infection in terms of endothelial immune activation [34,37,38] and among them, CCL2, CCL5, CCL20, CXCL1, CXCL10, CXCL11, TNF-α and ICAM-1 have been reported to be produced directly by DENV-infected microvascular endothelial cells [39]. The precision and reproducibility of the assays were assured by calculating the coefficient of variance of the replicates.…”

Section: Cytokine Profilingmentioning

confidence: 99%

Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection

et al. 2020

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Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.

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Dengue fatal cases present virus-specific HMGB1 response in peripheral organs

Cited by 24 publications

References 74 publications

Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway

Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue

Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection

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