ArticleRespiratory research2012
Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus.
Article in Respiratory research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 152 citations in OpenAlex.
- Review
- Vanin-1 deficiency enhances host tolerance to influenza infection by modulating cellular redox status.PNAS nexus · 2026Article
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- Stiffness-dependent alveolar type II cell senescence in idiopathic pulmonary fibrosis.Cell communication and signaling : CCS · 2026Article
- Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections.Archives of microbiology · 2026Review
- The Dual Role of Nrf2 Signaling in Virus Infections: Antiviral Guardian or Proviral Accomplice?Pathogens (Basel, Switzerland) · 2025Review
- High-throughput isolation of normal and pulmonary fibrosis human alveolar epithelial cells.Scientific reports · 2025Article
- Age Matters: Key Contributors to Interferon Toxicity in Infants During Influenza Virus Infection.Viruses · 2025Review
- Porcine reproductive and respiratory syndrome virus nsp5 inhibits the activation of the Nrf2/HO-1 pathway by targeting p62 to antagonize its antiviral activity.Journal of virology · 2025Article
- African swine fever virus enhances viral replication by increasing intracellular reduced glutathione levels, which suppresses stress granule formation.Veterinary research · 2024Article
- Nrf2 Regulates Inflammation by Modulating Dendritic Cell-T Cell Crosstalk during Viral-Bacterial Superinfection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus.International journal of molecular sciences · 2024Article
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- The pathogenesis of influenza in intact alveoli: virion endocytosis and its effects on the lung's air-blood barrier.Frontiers in immunology · 2024Review
- The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.Pathogens (Basel, Switzerland) · 2023Review
- NRF2 activators inhibit influenza A virus replication by interfering with nucleo-cytoplasmic export of viral RNPs in an NRF2-independent manner.PLoS pathogens · 2023Article
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Inflammatory cell death: how macrophages sense neighbouring cell infection and damage.Biochemical Society transactions · 2023Review
- Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundInfluenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes.
methodsAlveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively.
resultsWe found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels.
conclusionsOur results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.
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