ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 88 citations in OpenAlex.
- Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression.International journal of molecular sciences · 2016Trial
- Cytokine Concentrations in Plasma from Children with Severe and Non-Severe Community Acquired Pneumonia.PloS one · 2015Trial
- Hepatocyte growth factor/c-Met signaling axis in human diseases: Mechanistic insights and therapeutic potential.Journal of cell communication and signaling · 2026Review
- Neutrophil Plasticity in Airway Disease: Balancing Damage and Repair.Journal of innate immunity · 2026Review
- Bioprinted Ventilated 3D Alveoliform Epithelial Sacculoids.Research square · 2025Article
- The Originally Established PBE Cell Line as a Reliable In Vitro Model for Investigating SIV Infection and Immunity.International journal of molecular sciences · 2025Article
- Identification of inflammatory protein biomarkers for predicting the different subtype of adult with tuberculosis: an Olink proteomic study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Peripheral blood cytokine expression levels and their clinical significance in children with influenza.Translational pediatrics · 2025Article
- New analogs of 5-substituted-2(1Acta biochimica Polonica · 2025Article
- c-Met inhibitor NVP-BVU972 induces antiviral protection and suppresses NF-κB-mediated inflammation.Frontiers in immunology · 2025Article
- Serum T2-High Inflammation Mediators in Eosinophilic COPD.Biomolecules · 2024Article
- Anti-Influenza A Potential ofInternational journal of molecular sciences · 2024Article
- Novel Serum Biomarkers for Patients with Allergic Asthma Phenotype.Biomedicines · 2024Article
- EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.Cancer discovery · 2024Article
- Early transcriptomic changes at the skin interface during Powassan virus transmission byFrontiers in immunology · 2024Article
- The pathogenesis of influenza in intact alveoli: virion endocytosis and its effects on the lung's air-blood barrier.Frontiers in immunology · 2024Review
- RKIP suppresses the influenza A virus‑induced airway inflammatory response via the ERK/MAPK pathway.International journal of molecular medicine · 2023Article
- Impact of e-cigarette aerosol on primary human alveolar epithelial type 2 cells.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis.Military Medical Research · 2022Review
- Fostering experimental and computational synergy to modulate hyperinflammation.Trends in immunology · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The most severe complication of influenza is viral pneumonia, which can lead to the acute respiratory distress syndrome. Alveolar epithelial cells (AECs) are the first cells that influenza virus encounters upon entering the alveolus. Infected epithelial cells produce cytokines that attract and activate neutrophils and macrophages, which in turn induce damage to the epithelial-endothelial barrier. Hepatocyte growth factor (HGF)/c-Met and transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) are well known to regulate repair of damaged alveolar epithelium by stimulating cell migration and proliferation. Recently, TGF-α/EGFR signaling has also been shown to regulate innate immune responses in bronchial epithelial cells. However, little is known about whether HGF/c-Met signaling alters the innate immune responses and whether the innate immune responses in AECs are regulated by HGF/c-Met and TGF-α/EGFR. We hypothesized that HGF/c-Met and TGF-α/EGFR would regulate innate immune responses to influenza A virus infection in human AECs. We found that recombinant human HGF (rhHGF) and rhTGF-α stimulated primary human AECs to secrete IL-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) strongly and IL-6 and monocyte chemotactic protein 1 moderately. Influenza infection stimulated the secretion of IL-8 and GM-CSF by AECs plated on rat-tail collagen through EGFR activation likely by TGF-α released from AECs and through c-Met activated by HGF secreted from lung fibroblasts. HGF secretion by fibroblasts was stimulated by AEC production of prostaglandin E2 during influenza infection. We conclude that HGF/c-Met and TGF-α/EGFR signaling enhances the innate immune responses by human AECs during influenza infections.
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