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A neutrophil elastase inhibitor prevents bleomycin-induced pulmonary fibrosis in mice
Open accessAbstract
Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil elastase inhibitor, sivelestat, could alleviate pulmonary fibrosis; however, the antifibrotic mechanisms have not yet been clarified. We examined the antifibrotic mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, in this study. To elucidate the antifibrotic mechanisms of sivelestat, we examined a murine model of bleomycin-induced early-stage pulmonary fibrosis. After intratracheal instillation of bleomycin, sivelestat was administered intraperitoneally once a day for 7 or 14 days. Bronchoalveolar lavage fluid and lung samples were examined on day 7 or day 14 after bleomycin instillation. In the bleomycin-induced early-stage pulmonary fibrosis model, the neutrophil elastase level was increased in the lungs. Sivelestat significantly inhibited the increase in lung collagen content, fibrotic changes, the numbers of total cells (including macrophages, neutrophils and lymphocytes), the levels of the active form of TGF-β1 and phospho-Smad2 in bleomycin-induced early-stage pulmonary fibrosis. The total TGF-β1 levels and relative changes of TGF-β1 mRNA expression, however, were not decreased significantly by sivelestat. These results suggest that sivelestat alleviated bleomycin-induced pulmonary fibrosis via inhibition of both TGF-β activation and inflammatory cell recruitment in the lung.
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“Furthermore, pharmacological inhibition of neutrophil elastase by sivelestat protects mice from bleomycin induced lung fibrosis (167), demonstrating that at least in lungs, neutrophil elastase is pro-fibrotic.”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [167]
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Neutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268
Has Mortality from Acute Respiratory Distress Syndrome Decreased over Time?: A Systematic Review
Phua, J., Badia, J., Adhikari, N. K. J., Friedrich, J. O., Fowler, R., Singh, J. M., Scales, D. C., Stather, D. R., Li, A., Jones, A., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200805-722oc · Cited by 756
TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT)
Kasai, H., Allen, J. T., Mason, R. M., Kamimura, T., & Zhang, Z. (2005) · Respiratory Research · doi:10.1186/1465-9921-6-56 · Cited by 744
Gasse, P., Mary, C., Guénon, I., Noulin, N., Charron, S., Schnyder‐Candrian, S., Schnyder, B., Akira, S., Quesniaux, V. F. J., Lagente, V., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32285 · Cited by 503
Targeted Injury of Type II Alveolar Epithelial Cells Induces Pulmonary Fibrosis
Sisson, T. H., Mendez, M. P., Choi, K., Subbotina, N., Courey, A. J., Cunningham, A. K., Dave, A., Engelhardt, J. F., Liu, X., White, E. S., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200810-1615oc · Cited by 483
Kessenbrock, K., Fröhlich, L. F., Sixt, M., Lämmermann, T., Pfister, H., Bateman, A., Belaaouaj, A., Ring, J., Ollert, M. W., Fässler, R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34694 · Cited by 363
Scotton, C. J., Krupiczojc, M. A., Königshoff, M., Mercer, P. F., Lee, G., Kaminski, N., Morser, J., Post, J. M., Maher, T. M., Nicholson, A. G., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci33288 · Cited by 318
Fibroproliferation Occurs Early in the Acute Respiratory Distress Syndrome and Impacts on Outcome
Marshall, R. P., Bellingan, G. J., Webb, S., Puddicombe, A., Goldsack, N., McAnulty, R. J., & Laurent, G. J. (2000) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.162.5.2001061 · Cited by 281
Early Detection of Type III Procollagen Peptide in Acute Lung Injury
Chesnutt, A. N., Matthay, M. A., Tibayan, F. A., & Clark, J. G. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.3.9701124 · Cited by 268
Disorders of lung matrix remodeling
Chapman, H. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20729 · Cited by 225
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Matson, S. M., Ngo, L. T., Sugawara, Y., Fernando, V., Lugo, C., Kaczorowski-Worthley, A., Azeem, I., Harrison, A., Alsup, A., Schueddig, E., et al. (2025) · iScience · doi:10.1016/j.isci.2025.114125 · Cited by 5
Sharma, N., Nagaraj, C., Nagy, B. M., Marsh, L. M., Bordag, N., Zabini, D., Wygrecka, M., Klepetko, W., Gschwandtner, E., Genové, G., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179342 · Cited by 5
Kartamihardja, A. A. P., Amalia, S. N., Sekiguchi, A., Bhattarai, A., Taketomi-Takahashi, A., Motegi, S., Koyama, H., & Tsushima, Y. (2021) · PLoS ONE · doi:10.1371/journal.pone.0259211 · Cited by 5
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Mohning, M. P., Downey, G. P., Cosgrove, G. P., & Redente, E. F. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-54431-3.00003-2 · Cited by 6
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Morey, M. G., Illanad, G. H., & Rasool, M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1754620 · Cited by 2
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Suzuki, T., Sakurai, M., Suzuki, H., & Kawamura, T. (2023) · Journal of Nippon Medical School · doi:10.1272/jnms.jnms.2023_90-109 · Cited by 2
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Armani, E., Rizzi, A., Miglietta, D., Bassanetti, I., Amadei, F., Brogin, G., Capaldi, C., Rancati, F., Carnini, C., Fernandez, S. X., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02638 · Cited by 1
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Wu, C., Chen, X., Zhou, J., Wang, H., Huang, X., Tang, X., Cao, Z., & Ding, B. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108169 · Cited by 1
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Nakayama, S., Kanamori, A., Ikawa, T., Kamiya, K., Kudo, K., Yanagiya, R., Shimizu, T., Miki, Y., Nagasaki, Y., Araki, M., et al. (2026) · Science Advances · doi:10.1126/sciadv.adr9135 · Cited by 1
Volder, J. D., Bontinck, A., Haelterman, V., Boon, L., Joos, G., Brusselle, G., & Maes, T. (2025) · Respiratory Research · doi:10.1186/s12931-024-03082-9 · Cited by 1
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Ruhland, S., Nikolatou, K., Bridgeman, V. L., Rizou, T., Sahai, E. A., Bordoloi, J., Nolan, E., Elósegui-Artola, A., & Malanchi, I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.22.684057 · Cited by 1
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Khan, M. M. (2020) · Current Immunology Reviews · doi:10.2174/1573395516999200914143054
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拜, 克. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.142320
Wegrzyniak, O., Ekbom, E., Ellingsen, J., Eriksson, O., Lubberink, M., Malinovschi, A., Sigfridsson, J., Velikyan, I., Wilson, V., Emilsson, Ö. I., et al. (2025) · medRxiv · doi:10.1101/2025.06.18.25329561
Ahmed, S. W., Gogoi, D., Forde, L., Niu, M., Baird, R., McCarthy, C., Keane, M. P., McGrath, E. E., & Reeves, E. P. (2025) · Journal of Innate Immunity · doi:10.1159/000547814
Barbosa-Matos, C., Borges-Pereira, C., Libório‐Ramos, S., Fernandes, R., Oliveira, M., Mendes‐Frias, A., Silvestre, R., Osório, N. S., Bastos, H. N., Santos, R. F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26737863
Barbosa-Matos, C., Borges-Pereira, C., Libório‐Ramos, S., Fernandes, R., Oliveira, M., Mendes‐Frias, A., Silvestre, R., Osório, N. S., Bastos, H. N., Santos, R. F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26737860
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Monge, C., Majumder, N., Cumming, R. I., Mazumder, H. H., Li, Y., Goldsmith, W. T., Mahavithana, P., Ranpara, A. C., Tighe, R. M., Harkema, J. R., et al. (2026) · Particle and Fibre Toxicology · doi:10.1186/s12989-026-00686-5
Singh, S., Jaiswal, A., Dutta, J., Ray, A., Sengupta, S., Dey, S., Bandyopadhyay, A., Jaisankar, P., & Mabalirajan, U. (2026) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2026.102434
Lang, C., Wu, J., & Wang, N. (2026) · Molecular Genetics and Genomics · doi:10.1007/s00438-026-02473-5
Yang, L., Huang, Y., Liu, A., Yan, Y., Liu, B., & Yuan, X. (2026) · Biomedicines · doi:10.3390/biomedicines14102265
Metadata
- Authors
- Takemasa, A., Ishii, Y., & Fukuda, T.
- Affiliations
- Dokkyo Medical University (JP)
- Dokkyo University (JP)
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2012-03-22
- Volume
- 40
- Issue
- 6
- Pages
- 1475-1482
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W2137335759
- Cited by
- 140
- References
- 28
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 13 · 2023: 10 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 8 · 2013: 3 · 2012: 3
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- neutrophil elastase, sivelestat, pulmonary fibrosis, bleomycin-induced lung injury, TGF-β1 activation, Smad2 phosphorylation, lung inflammation, antifibrotic mechanism, collagen deposition, neutrophil elastase inhibitor
- MeSH terms
- Animals, Bleomycin, Collagen, Fibrosis, Glycine, Inflammation, Lung, Male, Mice, Inbred C57BL, Phosphorylation, Pulmonary Fibrosis, Sulfonamides, Time Factors, Serine Proteinase Inhibitors, Bronchoalveolar Lavage, Leukocyte Elastase, Mice, Smad2 Protein, Transforming Growth Factor beta1
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