دورية أكاديمية
Respiratory Syncytial Virus Infection Promotes Necroptosis and HMGB1 Release by Airway Epithelial Cells.
| العنوان: | Respiratory Syncytial Virus Infection Promotes Necroptosis and HMGB1 Release by Airway Epithelial Cells. |
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| المؤلفون: | Simpson J; QIMR Berghofer Medical Research Institute, Herston, Australia.; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia., Loh Z; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia., Ullah MA; QIMR Berghofer Medical Research Institute, Herston, Australia.; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia., Lynch JP; QIMR Berghofer Medical Research Institute, Herston, Australia.; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia., Werder RB; QIMR Berghofer Medical Research Institute, Herston, Australia.; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia., Collinson N; QIMR Berghofer Medical Research Institute, Herston, Australia., Zhang V; QIMR Berghofer Medical Research Institute, Herston, Australia.; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia., Dondelinger Y; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Bertrand MJM; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Everard ML; School of Medicine and., Blyth CC; School of Medicine and.; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.; Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia.; Department of Microbiology, PathWest Laboratory Medicine WA, QEII Medical Centre, Perth, Western Australia, Australia., Hartel G; QIMR Berghofer Medical Research Institute, Herston, Australia., Van Oosterhout AJ; GlaxoSmithKline, Stevenage, United Kingdom., Gough PJ; GlaxoSmithKline, Philadelphia, Pennsylvania., Bertin J; GlaxoSmithKline, Philadelphia, Pennsylvania., Upham JW; University of Queensland Diamantina Institute, Brisbane, Queensland, Australia.; Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia; and., Spann KM; Queensland University of Technology, Brisbane, Queensland, Australia., Phipps S; QIMR Berghofer Medical Research Institute, Herston, Australia.; School of Biomedical Science, University of Queensland, Brisbane, Queensland, Australia.; Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia; and. |
| المصدر: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2020 Jun 01; Vol. 201 (11), pp. 1358-1371. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 9421642 Publication Model: Print Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : New York, NY : American Thoracic Society Original Publication: New York, NY : American Lung Association, c1994- |
| مواضيع طبية MeSH: | Necroptosis*, Bronchiolitis/*virology , Epithelial Cells/*metabolism , Epithelial Cells/*pathology , HMGB1 Protein/*metabolism , Respiratory Mucosa/*cytology , Respiratory Syncytial Virus Infections/*metabolism, Animals ; Child, Preschool ; Humans ; Infant ; Mice ; Prospective Studies |
| مستخلص: | Rationale : Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown. Objectives : To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via HMGB1 (high mobility group box 1) release. Methods : Nasopharyngeal samples were collected from children presenting to the hospital with acute respiratory infection. Primary human AECs and neonatal mice were inoculated with RSV and murine Pneumovirus , respectively. Necroptosis was determined via viability assays and immunohistochemistry for RIPK1 (receptor-interacting protein kinase-1), MLKL (mixed lineage kinase domain-like pseudokinase) protein, and caspase-3. Necroptosis was blocked using pharmacological inhibitors and RIPK1 kinase-dead knockin mice. Measurements and Main Results : HMGB1 levels were elevated in nasopharyngeal samples of children with acute RSV infection. RSV-induced epithelial cell death was associated with increased phosphorylated RIPK1 and phosphorylated MLKL but not active caspase-3 expression. Inhibition of RIPK1 or MLKL attenuated RSV-induced HMGB1 translocation and release, and lowered viral load. MLKL inhibition increased active caspase-3 expression in a caspase-8/9-dependent manner. In susceptible mice, Pneumovirus infection upregulated RIPK1 and MLKL expression in the airway epithelium at 8 to 10 days after infection, coinciding with AEC sloughing, HMGB1 release, and neutrophilic inflammation. Genetic or pharmacological inhibition of RIPK1 or MLKL attenuated these pathologies, lowered viral load, and prevented type 2 inflammation and airway remodeling. Necroptosis inhibition in early life ameliorated asthma progression induced by viral or allergen challenge in later life. Conclusions : Pneumovirus infection induces AEC necroptosis. Inhibition of necroptosis may be a viable strategy to limit the severity of viral bronchiolitis and break its nexus with asthma. |
| التعليقات: | Comment in: Am J Respir Crit Care Med. 2020 Jun 1;201(11):1321-1323. (PMID: 32182121) |
| فهرسة مساهمة: | Keywords: MLKL; Pneumovirus; asthma; bronchiolitis; necroptosis |
| المشرفين على المادة: | 0 (HMGB1 Protein) |
| تواريخ الأحداث: | Date Created: 20200228 Date Completed: 20200820 Latest Revision: 20200820 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1164/rccm.201906-1149OC |
| PMID: | 32105156 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-4970 |
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| DOI: | 10.1164/rccm.201906-1149OC |