ArticleThe Journal of biological chemistry2013
Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial cells via protein kinase signaling and reactive oxygen species.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- ROSBASE1.0: a comprehensive database of reactive oxygen species (ROS): categorization of cell organelles, proteins, taxonomy, and diseases based on ROS-related activities.Database : the journal of biological databases and curation · 2025Article
- Mycobacterium tuberculosis inhibits METTL14-mediated mCell discovery · 2024Article
- An Oxygen Supply Strategy for Sonodynamic Therapy in Tuberculous Granuloma Lesions Using a Catalase-Loaded Nanoplatform.International journal of nanomedicine · 2023Article
- Article
- A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium-Host Interaction.Cells · 2021Review
- Neutrophils in Tuberculosis: Cell Biology, Cellular Networking and Multitasking in Host Defense.International journal of molecular sciences · 2021Review
- The Roles of Inflammasomes in Host Defense againstPathogens (Basel, Switzerland) · 2021Review
- TLR-9 Plays a Role inFrontiers in immunology · 2021Article
- Evolution of Drug-ResistantFrontiers in microbiology · 2021Review
- Bacterial extracellular vesicles isolated from organic dust induce neutrophilic inflammation in the lung.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- CFD simulations for paper-based DNA amplification reaction (LAMP) of Mycobacterium tuberculosis-point-of-care diagnostic perspective.Medical & biological engineering & computing · 2020Article
- Article
- Comparative analysis of homologous aminopeptidase PepN from pathogenic and non-pathogenic mycobacteria reveals divergent traits.PloS one · 2019Article
- Tuberculosis-associated IgA nephropathy.The Journal of international medical research · 2018Review
- Article
- Role of ESAT-6 in renal injury by regulating microRNA-155 expression via TLR4/MyD88 signaling pathway in mice withBioscience reports · 2017Article
- Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3.Scientific reports · 2017Article
- Two-Component Signal Transduction Systems of Pathogenic Bacteria As Targets for Antimicrobial Therapy: An Overview.Frontiers in microbiology · 2017Review
- Integrating gene set analysis and nonlinear predictive modeling of disease phenotypes using a Bayesian multitask formulation.BMC bioinformatics · 2016Article
- Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?Journal of innate immunity · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis is critical for the virulence and pathogenicity of M. tuberculosis. IL-8, a major chemotactic cytokine for neutrophils and T lymphocytes, plays important roles in the development of lung injury. To further understand the role of ESAT-6 in lung pathology associated with tuberculosis development, we studied the effects of ESAT-6 on the regulation of IL-8 expression in lung epithelial cells. ESAT-6 induced IL-8 expression by increasing IL-8 gene transcription and mRNA stability. ESAT-6 induction of IL-8 promoter activity was dependent on nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) binding and sensitive to pharmacological inhibition of PKC and ERK and p38 MAPK pathways. ESAT-6 activated ERK and p38 MAPK phosphorylation and rapidly induced reactive oxygen species (ROS) production. Dimethylthiourea but not mannitol inhibited IL-8 induction by ESAT-6, further supporting the involvement of ROS in the induction of IL-8 expression. Exposure of mice to ESAT-6 induced localized inflammatory cell aggregate formation with characteristics of early granuloma concomitant with increased keratinocyte chemoattractant CXCL1 staining in bronchiolar and alveolar type II epithelial cells and alveolar macrophages. Our studies have identified a signal transduction pathway involving ROS, PKC, ERK, and p38 MAPKs and NF-κB and AP-1 in the ESAT-6 induction of IL-8 expression in lung epithelial cells. This has important implications for the understanding of lung innate immune responses to tuberculosis and the pathogenesis of lung injury in tuberculosis.
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Registered trials
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