ArticlePloS one2010
Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 106 citations in OpenAlex.
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- Immunomodulatory Effects of Nintedanib on Human Blood Monocytes/Macrophages from Patients with Idiopathic Pulmonary Fibrosis.Biomolecules · 2026Article
- Neutrophil Heterogeneity in Airway Inflammatory Diseases.Inflammation · 2025Review
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- The Intersection between Immune System and Idiopathic Pulmonary Fibrosis-A Concise Review.Fibrosis (Hong Kong, China) · 2025Article
- Towards predicting implant-induced fibrosis: A standardized network model of macrophage-fibroblast interactions.Computational and structural biotechnology journal · 2025Article
- Fibroblast Yap/Taz Signaling in Extracellular Matrix Homeostasis and Tissue Fibrosis.Journal of clinical medicine · 2024Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- The Effect ofJournal of experimental pharmacology · 2024Article
- Article
- The Role of Immune Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis.Medicina (Kaunas, Lithuania) · 2023Review
- Molecular mechanisms and treatment responses of pulmonary fibrosis in severe COVID-19.Respiratory research · 2023Article
- Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages.iScience · 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
- Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis.Frontiers in immunology · 2023Article
- Epithelial cells/progenitor cells in developing human lower respiratory tract: Characterization and transplantation to rat model of pulmonary injury.BioImpacts : BI · 2023Article
- Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Lung fibrogenic microenvironment in mouse reconstitutes human alveolar structure and lung tumor.iScience · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMatrix metalloproteinases (MMPs) may have pro and antifibrotic roles within the lungs, due to its ability to modulate collagen turnover and immune mediators. MMP-8 is a collagenase that also cleaves a number of cytokines and chemokines. METHODOLOGY AND PRINCIPAL
findingsTo evaluate its relevance in lung fibrosis, wildtype and Mmp8(-/-) mice were treated with either intratracheal bleomycin or saline, and lungs were harvested at different time points. Fibrosis, collagen, collagenases, gelatinases, TGFβ and IL-10 were measured in lung tissue. Mmp8(-/-) mice developed less fibrosis than their wildtype counterparts. This was related to an increase in lung inflammatory cells, MMP-9 and IL-10 levels in these mutant animals. In vitro experiments showed that MMP-8 cleaves murine and human IL-10, and tissue from knockout animals showed decreased IL-10 processing. Additionally, lung fibroblasts from these mice were cultured in the presence of bleomycin and collagen, IL-10 and STAT3 activation (downstream signal in response to IL-10) measured by western blotting. In cell cultures, bleomycin increased collagen synthesis only in wildtype mice. Fibroblasts from knockout mice did not show increased collagen synthesis, but increased levels of unprocessed IL-10 and STAT3 phosphorylation. Blockade of IL-10 reverted this phenotype, increasing collagen in cultures.
conclusionsAccording to these results, we conclude that the absence of MMP-8 has an antifibrotic effect by increasing IL-10 and propose that this metalloprotease could be a relevant modulator of IL-10 metabolism in vivo.
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