Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C
| العنوان: | Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C |
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| المؤلفون: | Cheng-Lun Na, Hector R. Wong, Timothy E. Weaver, James P. Bridges, Yan Xu |
| المصدر: | The Journal of Cell Biology |
| بيانات النشر: | Rockefeller University Press, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Protein Folding, Leupeptins, Gene Expression, Apoptosis, medicine.disease_cause, Mice, 0302 clinical medicine, NF-KappaB Inhibitor alpha, Research Articles, 0303 health sciences, Mutation, Caspase 3, Nuclear Proteins, Transfection, Immunohistochemistry, Pulmonary Surfactant-Associated Protein C, Respiratory Syncytial Viruses, Up-Regulation, 3. Good health, DNA-Binding Proteins, Caspases, I-kappa B Proteins, Oligopeptides, Proteasome Inhibitors, Proteasome Endopeptidase Complex, Cell Survival, Down-Regulation, Mice, Transgenic, Regulatory Factor X Transcription Factors, Protein Sorting Signals, Biology, Article, Cell Line, 03 medical and health sciences, Downregulation and upregulation, medicine, Animals, Humans, Genetic Predisposition to Disease, Pulmonary surfactant-associated protein C, 030304 developmental biology, Gene Expression Profiling, Endoplasmic reticulum, Lysosome-Associated Membrane Glycoproteins, NF-kappa B p50 Subunit, Epithelial Cells, Surfactant protein C, Cell Biology, Molecular biology, 030228 respiratory system, Unfolded protein response, Lung Diseases, Interstitial, Peptides, Transcription Factors |
| الوصف: | Mutations in the gene encoding SP-C (surfactant protein C; SFTPC) have been linked to interstitial lung disease (ILD) in children and adults. Expression of the index mutation, SP-C(Deltaexon4), in transiently transfected cells and type II cells of transgenic mice resulted in misfolding of the proprotein, activation of endoplasmic reticulum (ER) stress pathways, and cytotoxicity. In this study, we show that stably transfected cells adapted to chronic ER stress imposed by the constitutive expression of SP-C(Deltaexon4) via an NF-kappaB-dependent pathway. However, the infection of cells expressing SP-C(Deltaexon4) with respiratory syncytial virus resulted in significantly enhanced cytotoxicity associated with accumulation of the mutant proprotein, pronounced activation of the unfolded protein response, and cell death. Adaptation to chronic ER stress imposed by misfolded SP-C was associated with increased susceptibility to viral-induced cell death. The wide variability in the age of onset of ILD in patients with SFTPC mutations may be related to environmental insults that ultimately overwhelm the homeostatic cytoprotective response. |
| تدمد: | 1540-8140 0021-9525 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d99b281b52249f8eb354cab3c913854fTest https://doi.org/10.1083/jcb.200508016Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d99b281b52249f8eb354cab3c913854f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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