ArticlePloS one2016
HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- A bovine pulmosphere model and multiomics reveal early host response signature in tuberculosis.Communications biology · 2025Article
- Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients.Biomedicines · 2023Article
- Immunogenic cell death in cancer immunotherapy.BMB reports · 2023Review
- Pyroptosis and respiratory diseases: A review of current knowledge.Frontiers in immunology · 2022Review
- Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It?Frontiers in microbiology · 2021Review
- Decreased Expression of the High Mobility Group Box 1 (Microorganisms · 2020Article
- RNA Sensing ofVaccines · 2020Review
- Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment.Mediators of inflammation · 2020Review
- Household Contacts of Leprosy Patients in Endemic Areas Display a Specific Innate Immunity Profile.Frontiers in immunology · 2020Article
- Paradoxical Roles of the MAL/Tirap Adaptor in Pathologies.Frontiers in immunology · 2020Review
- Systemic RAGE ligands are upregulated in tuberculosis individuals with diabetes co-morbidity and modulated by anti-tuberculosis treatment and metformin therapy.BMC infectious diseases · 2019Article
- The Role of HMGB1, a Nuclear Damage-Associated Molecular Pattern Molecule, in the Pathogenesis of Lung Diseases.Antioxidants & redox signaling · 2019Review
- HIV Infection Functionally Impairs Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses.Journal of virology · 2019Article
- Inflammation-Related Patterns in the Clinical Staging and Severity Assessment of Chronic Kidney Disease.Disease markers · 2019Article
- Article
- Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin DBMC infectious diseases · 2018Article
- Inflammasomes: Pandora's box for sepsis.Journal of inflammation research · 2018Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB).
methodsA prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo.
resultsIn active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6-15.1) vs 3.6(3.6-3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001), severity-score (rs +0.317, P = 0.004), and fever and hospitalization durations (rs +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan.
conclusionIn patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control.
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