ArticleRespiratory research2019
Interferon-γ enhances the antifibrotic effects of pirfenidone by attenuating IPF lung fibroblast activation and differentiation.
Article in Respiratory research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
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- Targeting canonical TGFβ/SMAD3 and ERK1/2 signaling in human valve interstitial cells to modulate immune-fibrotic responses in rheumatic heart disease.Journal of physiology and biochemistry · 2026Article
- Evaluation and Comparison of Treatment with Polymerised Collagen or Pirfenidone as Stand-Alone Therapy on the Production of Profibrotic Factors in Tracheal Stenosis and Tracheal Anastomosis Scarring After Resection.International journal of molecular sciences · 2026Article
- Tweaking the Complex Fibrogenic Role of Lymphocytes in Idiopathic Pulmonary Fibrosis.Tuberculosis and respiratory diseases · 2026Article
- The role of immune cell crosstalk and signaling pathways in the pathogenesis of pulmonary fibrosis.Molecular biology reports · 2026Review
- An intricate relationship between fibrosis and autoimmune diseases: a specific focus on unraveling its molecular, immunological, and epigenetic drivers.Frontiers in immunology · 2026Review
- Progress in the Application of Pirfenidone in Post-COVID-19 Pulmonary Fibrosis: A Review.Cureus · 2025Review
- Variable steady inflammation and inflammatory responses in precision-cut lung slices from various IPF lung Regions.Respiratory research · 2025Article
- Diammonium Glycyrrhizinate Alleviated Myocardial Fibrosis Induced by Isoprenaline Via Modulation of STAT/Smad3 Pathway.Journal of cardiovascular translational research · 2025Article
- The Intricate Process of Calcification in Granuloma Formation and the Complications FollowingBiomolecules · 2025Review
- MK2 Inhibition in CD4+ T Cells Protects Against IFNγ and IL-17A, Chronic Inflammation, and Fibrosis in Inflammatory Bowel Disease Models.Inflammatory bowel diseases · 2025Article
- Safely Targeting Cancer, the Wound That Never Heals, Utilizing CBP/Beta-Catenin Antagonists.Cancers · 2025Article
- Evaluating the efficacy of ethanolic extract of Tapak Liman (Open veterinary journal · 2025Review
- The Impact of Psychological Stress on Wound Healing: Implications for Neocollagenesis and Scar Treatment Efficacy.Clinical, cosmetic and investigational dermatology · 2025Review
- Development of a fish oil-nanoemulsion gel as a drug-delivery system to prevent capsular contracture.Scientific reports · 2024Article
- Article
- Understanding myofibroblast origin in the fibrotic lung.Chinese medical journal pulmonary and critical care medicine · 2024Review
- EphB2 Receptor Promotes Dermal Fibrosis in Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Role of telomere dysfunction and immune infiltration in idiopathic pulmonary fibrosis: new insights from bioinformatics analysis.Frontiers in genetics · 2024Article
- Cytokine correlations in childhood-onset rheumatic diseases with pulmonary involvement.Frontiers in pediatrics · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) pathogenesis involves multiple pathways, and combined antifibrotic therapy is needed for future IPF therapy. Inhaled interferon-γ (IFN-γ) was recently shown to be safe and without systemic effects in patients with IPF.
aimTo examine the in vitro effects of individual and combined treatment with IFN-γ and pirfenidone (PFD) on normal and IPF fibroblast activation and extracellular matrix remodeling after TGF-β1 and PDGF-BB stimulation.
methodsIPF and normal human lung fibroblasts (NHLF) were treated with IFN-γ, PFD or a combination of both drugs in the presence of either TGF-β1 or PDGF-BB. The effects of TGF-β1 and PDGF-BB treatment on cell viability, proliferation, differentiation and migration were examined. The expression of collagen 1, matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs) was analyzed using qPCR, Western blotting and gelatin zymography. Total collagen content in conditioned media was also measured using a Sircol assay.
resultsCompared to that of PFD, the effect of IFN-γ in downregulating normal and IPF lung fibroblast differentiation to myofibroblasts in response to TGF-β1 was more potent. Importantly, the combination of IFN-γ and PFD had a possibly synergistic/additive effect in inhibiting the TGF-β1- and PDGF-BB-induced proliferation, migration and differentiation of normal and IPF lung fibroblasts. Furthermore, both drugs reversed TGF-β1-induced effects on MMP-1, - 2, - 3, - 7, and - 9, while only PFD promoted TIMP-1 and-2 expression and release.
conclusionsOur findings demonstrate that the antifibrotic effects of IFN-γ and PFD on normal and IPF lung fibroblasts are different and complementary. Combination therapy with inhaled IFN-γ and PFD in IPF is promising and should be further explored in IPF clinical trials.
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