ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Profibrotic activities for matrix metalloproteinase-8 during bleomycin-mediated lung injury.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 91 citations in OpenAlex.
- Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis.PloS one · 2019Trial
- Matrix Metalloproteinase-8 Deficiency Alters the Balance Between Viral Clearance and Immunopathology in H1N1 Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Targeted LNP-mediated delivery of VE-cadherin mRNA reduces vascular hyperpermeability in vivo.Blood advances · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Neutrophil Heterogeneity in Airway Inflammatory Diseases.Inflammation · 2025Review
- Association of salivary mmp-8 gene polymorphism with its protein expression in oral submucous fibrosis patients.Odontology · 2025Article
- Exploring diagnostic gene markers and immune infiltration in idiopathic pulmonary fibrosis.Journal of thoracic disease · 2025Article
- A 23-Plex Cytokine/Chemokine Analysis Identifies TNFRII, MMP-8, and sIL-1RII as Potential Biomarkers for Systemic Sclerosis.Biomedicines · 2025Article
- Extreme temperatures modulate gene expression in the airway epithelium of the lungs in mice and asthma patients.Frontiers in medicine · 2025Article
- Neutrophil dynamics in pulmonary fibrosis: pathophysiological and therapeutic perspectives.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Review
- Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis.Respiratory research · 2024Article
- The Effect ofJournal of experimental pharmacology · 2024Article
- Article
- Long-Term Radiological Pulmonary Changes in Mechanically Ventilated Patients with Respiratory Failure due to SARS-CoV-2 Infection.Biomedicines · 2023Article
- Molecular mechanisms and treatment responses of pulmonary fibrosis in severe COVID-19.Respiratory research · 2023Article
- Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression.International journal of molecular sciences · 2023Article
- Immune Mechanisms of Pulmonary Fibrosis with Bleomycin.International journal of molecular sciences · 2023Review
- The Role of Matrix Metalloproteinase in Inflammation with a Focus on Infectious Diseases.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Matrix metalloproteinase-8 (MMP-8) is a potent interstitial collagenase thought to be expressed mainly by polymorphonuclear neutrophils. To determine whether MMP-8 regulates lung inflammatory or fibrotic responses to bleomycin, we delivered bleomycin by the intratracheal route to wild-type (WT) versus Mmp-8(-/-) mice and quantified MMP-8 expression, and inflammation and fibrosis in the lung samples. Mmp-8 steady state mRNA and protein levels increase in whole lung and bronchoalveolar lavage samples when WT mice are treated with bleomycin. Activated murine lung fibroblasts express Mmp-8 in vitro. MMP-8 expression is increased in leukocytes in the lungs of patients with idiopathic pulmonary fibrosis compared with control lung samples. Compared with bleomycin-treated WT mice, bleomycin-treated Mmp-8(-/-) mice have greater lung inflammation, but reduced lung fibrosis. Whereas bleomycin-treated Mmp-8(-/-) and WT mice have similar lung levels of several pro- and antifibrotic mediators (TGF-β, IL-13, JE, and IFN-γ), Mmp-8(-/-) mice have higher lung levels of IFN-γ-inducible protein-10 (IP-10) and MIP-1α. Genetically deleting either Ip-10 or Mip-1α in Mmp-8(-/-) mice abrogates their lung inflammatory response to bleomycin, but reconstitutes their lung fibrotic response to bleomycin. Studies of bleomycin-treated Mmp-8 bone marrow chimeric mice show that both leukocytes and lung parenchymal cells are sources of profibrotic MMP-8 during bleomycin-mediated lung fibrosis. Thus, during bleomycin-mediated lung injury, MMP-8 dampens the lung acute inflammatory response, but promotes lung fibrosis by reducing lung levels of IP-10 and MIP-1α. These data indicate therapeutic strategies to reduce lung levels of MMP-8 may limit fibroproliferative responses to injury in the human lung.
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Registered trials
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.