ArticleRespiratory research2015
Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.
Article in Respiratory research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 126 citations in OpenAlex.
- DPEP1 promotes pulmonary fibrosis by regulating arachidonic acid metabolism.Journal of thoracic disease · 2026Article
- Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation.Biomaterials science · 2026Article
- Combined antagonism of Oncostatin M (OSM) and Interleukin 6 (IL-6) provides both anti-fibrotic and anti-inflammatory benefit in pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Divergent immune and extracellular matrix transcriptional programs underlie poor prognosis in early-stage lung adenocarcinoma.Frontiers in immunology · 2026Article
- Systemic miR-26a deficiency attenuates pulmonary fibrosis via PTEN upregulation and downstream TIMP-1 suppression.Molecular therapy. Nucleic acids · 2025Article
- Pharmacological inhibition of Epac1 protects against pulmonary fibrosis by blocking FoxO3a neddylation.The European respiratory journal · 2025Article
- Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation.bioRxiv : the preprint server for biology · 2025Article
- Cytokine Profiles of Bronchoalveolar Lavage in Patients with Interstitial Lung Diseases and Non-Allergic Asthma.International journal of molecular sciences · 2025Article
- Efficacy of umbelliferone-loaded nanostructured lipid carrier in the management of bleomycin-induced idiopathic pulmonary fibrosis: experimental and network pharmacology insight.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote IL6-dependent fibroblast activation.Cell biomaterials · 2025Article
- Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell.Advanced biology · 2025Review
- Cyclic mechanical loading of photopolymerized methacrylated hydrogels for probing interdependent effects of strain, stiffness, and substrate composition in pulmonary fibrogenesis.Scientific reports · 2025Article
- CD103+ dendritic cell-fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis.JCI insight · 2025Article
- Role of Interleukin-6 in Rheumatoid Arthritis-Associated Interstitial Lung Disease: Focus on the JAK/STAT Pathway and Macrophage Polarization.Journal of inflammation research · 2025Review
- Highly Calibrated Relationship Between Bleomycin Concentrations and Facets of the Active Phase Fibrosis in Classical Mouse Bleomycin Model.International journal of molecular sciences · 2024Article
- Direct M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote fibroblast activation.bioRxiv : the preprint server for biology · 2024Article
- Pharmacological expansion of type 2 alveolar epithelial cells promotes regenerative lower airway repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Perspectives on Post-COVID-19 Pulmonary Fibrosis Treatment.Journal of personalized medicine · 2023Review
- Review
- Oxy210, a Semi-Synthetic Oxysterol, Inhibits Profibrotic Signaling in Cellular Models of Lung and Kidney Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVarious signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis.
methodsMice received a single dose of 3 mg/kg body weight of bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi). Lung homogenates and sections from mice in the early inflammatory phase were subjected to phospho-protein array analysis and immunofluorescence studies, respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced lung injury was evaluated.
resultsPhospho-protein array revealed that BLM induced phosphorylation of molecules downstream of the IL-6 receptor such as Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2 pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2 pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was biphasic, with the first increase from 0.5 to 3 dpi followed by the second increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6-neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung fibrosis.
conclusionsThe present study demonstrated that IL-6 could play a bidirectional role in the pathogenesis of lung fibrosis. In particular, upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has antifibrotic activity through regulating the cell fate of type 2 pneumocytes in an autocrine/paracrine manner.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.