ArticleMolecular medicine (Cambridge, Mass.)2015
H5N1 Virus Hemagglutinin Inhibition of cAMP-Dependent CFTR via TLR4-Mediated Janus Tyrosine Kinase 3 Activation Exacerbates Lung Inflammation.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- The role of TLR4/NF-kB signaling axis in pneumonia: from molecular mechanisms to regulation by phytochemicals.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Viral Infection Correlates with a Better Clinical Outcome than Pulmonary Exacerbation of Bacterial Origin in Paediatric Patients with Cystic Fibrosis.Pathogens (Basel, Switzerland) · 2025Article
- Article
- SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular ClSignal transduction and targeted therapy · 2024Article
- Cell membrane-bound toll-like receptor-1/2/4/6 monomers and -2 heterodimer inhibit enterovirus 71 replication by activating the antiviral innate response.Frontiers in immunology · 2023Article
- Integrated Analysis of Non-Coding RNA and mRNA Expression Profiles in Exosomes from Lung Tissue with Sepsis-Induced Acute Lung Injury.Journal of inflammation research · 2023Article
- [Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Intestinal breast cancer resistance protein (BCRP) requires Janus kinase 3 activity for drug efflux and barrier functions in obesity.The Journal of biological chemistry · 2019Article
- Increased intracellular ClMucosal immunology · 2018Article
- Inhibition of miR-142-5P ameliorates disease in mouse models of experimental colitis.PloS one · 2017Article
- The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?American journal of physiology. Lung cellular and molecular physiology · 2016Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The host tolerance mechanisms to avian influenza virus (H5N1) infection that limit tissue injury remain unknown. Emerging evidence indicates that cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl(-) channel, modulates airway inflammation. Janus tyrosine kinase (JAK) 3, a JAK family member that plays a central role in inflammatory responses, prominently contributes to the dysregulated innate immune response upon H5N1 attachment; therefore, this study aims to elucidate whether JAK3 activation induced by H5N1 hemagglutinin (HA) inhibits cAMP-dependent CFTR channels. We performed short-circuit current, immunohistochemistry and molecular analyses of the airway epithelium in Jak3(+/+) and Jak3(+/-) mice. We demonstrate that H5N1 HA attachment inhibits cAMP-dependent CFTR Cl(-) channels via JAK3-mediated adenylyl cyclase (AC) suppression, which reduces cAMP production. This inhibition leads to increased nuclear factor-kappa B (NF-κB) signaling and inflammatory responses. H5N1 HA is detected by TLR4 expressed on respiratory epithelial cells, facilitating JAK3 activation. This activation induces the interaction between TLR4 and Gαi protein, which blocks ACs. Our findings provide novel insight into the pathogenesis of acute lung injury via the inhibition of cAMP-dependent CFTR channels, indicating that the administration of cAMP-elevating agents and targeting JAK3 may activate host tolerance to infection for the management of influenza virus-induced fatal pneumonia.
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