ArticlePloS one2022
The lymphocyte-specific protein tyrosine kinase-specific inhibitor A-770041 attenuates lung fibrosis via the suppression of TGF-β production in regulatory T-cells.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- The role of immune cell crosstalk and signaling pathways in the pathogenesis of pulmonary fibrosis.Molecular biology reports · 2026Review
- Downregulation of the CCK-B Receptor in Pancreatic Stellate Cells Blocks Molecular Proliferative Pathways and Increases Apoptosis to Decrease Pancreatic Cancer Growth In Vitro.International journal of molecular sciences · 2025Article
- T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025Review
- CD4Frontiers in immunology · 2025Review
- Review
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
- Interferon autoantibodies as signals of a sick thymus.Frontiers in immunology · 2024Review
- Drug therapy for myocarditis induced by immune checkpoint inhibitors.Frontiers in pharmacology · 2023Review
- Longitudinal drug synergy assessment using convolutional neural network image-decoding of glioblastoma single-spheroid cultures.Neuro-oncology advancesArticle
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLymphocyte-specific protein tyrosine kinase (Lck) is a member of the Src family of tyrosine kinases. The significance of Lck inhibition in lung fibrosis has not yet been fully elucidated, even though lung fibrosis is commonly preceded by inflammation caused by infiltration of T-cells expressing Lck. In this study, we examined the effect of Lck inhibition in an experimental mouse model of lung fibrosis. We also evaluated the effect of Lck inhibition on the expression of TGF-β1, an inhibitory cytokine regulating the immune function, in regulatory T-cells (Tregs).
methodsLung fibrosis was induced in mice by intratracheal administration of bleomycin. A-770041, a Lck-specific inhibitor, was administrated daily by gavage. Tregs were isolated from the lung using a CD4+CD25+ Regulatory T-cell Isolation Kit. The expression of Tgfb on Tregs was examined by flow cytometry and quantitative polymerase chain reaction. The concentration of TGF-β in bronchoalveolar lavage fluid (BALF) and cell culture supernatant from Tregs was quantified by an enzyme-linked immunosorbent assay.
resultsA-770041 inhibited the phosphorylation of Lck in murine lymphocytes to the same degree as nintedanib. A-770041 attenuated lung fibrosis in bleomycin-treated mice and reduced the concentration of TGF-β in BALF. A flow-cytometry analysis showed that A-770041 reduced the number of Tregs producing TGF-β1 in the lung. In isolated Tregs, Lck inhibition by A-770041 decreased the Tgfb mRNA level as well as the concentration of TGF-β in the supernatant.
conclusionsThese results suggest that Lck inhibition attenuated lung fibrosis by suppressing TGF-β production in Tregs and support the role of Tregs in the pathogenesis of lung fibrosis.
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