Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury
Open accessAbstract
Mesenchymal stem cells (MSCs) have been exploited as cellular vectors to treat a wide array of diseases but the mechanisms responsible for their therapeutic effect remain indeterminate. Previously, we reported that MSCs inhibit bleomycin (BLM)-induced inflammation and fibrosis within the lungs of mice. Interrogation of the MSC transcriptome identified interleukin 1 receptor antagonist (IL1RN) as a potential mediator of this effect. Fractionation studies indicated that MSCs are the principal source of IL1RN in murine bone marrow and that its expression is restricted to a unique subpopulation of cells. Moreover, MSC-conditioned media was shown to block proliferation of an IL-1α-dependent T cell line and inhibit production of TNF-α by activated macrophages in vitro . Studies conducted in mice revealed that MSC administration was more effective than recombinant IL1RN delivered via adenoviral infection or osmotic pumps in inhibiting BLM-induced increases in TNF-α, IL-1α, and IL1RN mRNA in lung, IL1RN protein in bronchoalveolar lavage (BAL) fluid, and trafficking of lymphocytes and neutrophils into the lung. Therefore, MSCs protect lung tissue from BLM-induced injury by blocking TNF-α and IL-1, two fundamental proinflammatory cytokines in lung. Identification of IL1RN-expressing human MSC subpopulations may provide a novel cellular vector for treating chronic inflammatory diseases in humans.
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IL-1RA-producing MSCs completely revert lung inflammation in mice by suppressing production of IL-1α, IL-1β and TNF-α by alveolar macrophages.
“In fact, IL-1RA-producing MSCs has completely reverted lung inflammation in mice by suppressing production of IL-1α, IL-1β and TNF-α by alveolar macrophages [74], [175].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [175]
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- Authors
- Ortiz, L. A., DuTreil, M., Fattman, C., Pandey, A. C., Torres, G., Go, K., & Phinney, D. G.
- Affiliations
- University of Pittsburgh (US)
- Tulane University (US)
- *Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-06-26
- Volume
- 104
- Issue
- 26
- Pages
- 11002-11007
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1891813
- OpenAlex
- W2133375451
- Cited by
- 1,019
- References
- 1
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 22 · 2023: 23 · 2022: 34 · 2021: 45 · 2020: 65 · 2019: 52 · 2018: 61 · 2017: 68 · 2016: 64 · 2015: 78 · 2014: 72 · 2013: 85 · 2012: 78
- FWCI
- 26.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL071953, P01HL075161)
- National Institute of Neurological Disorders and Stroke (R01-NS39033-01A2, R01-NS39033-02S1, R01NS039033)
- National Institute of Environmental Health Sciences (ES010859, R01ES010859)
- National Center for Research Resources (P40RR017447, P40 RR 17 447)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- interleukin-1 receptor antagonist, mesenchymal stem cells, lung injury, bleomycin-induced fibrosis, anti-inflammatory activity, antifibrotic effect, TNF-α, IL-1α, inflammatory cytokines, macrophages, T cell proliferation, lymphocyte migration, neutrophil trafficking, bone marrow, cell therapy
- MeSH terms
- Animals, Bone Marrow, Fibrosis, Inflammation, Lung Diseases, Male, Mice, Inbred BALB C, Tumor Necrosis Factor-alpha, Mice, Interleukin-1alpha, Interleukin 1 Receptor Antagonist Protein, Mesenchymal Stem Cells
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