دورية أكاديمية
The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.
| العنوان: | The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases. |
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| المؤلفون: | Kim, Hyelim, Park, Hee Ho, Kim, Hong Nam, Seo, Donghyuk, Hong, Kyung Soo, Jang, Jong Geol, Seo, Eun U, Kim, In-Young, Jeon, So-Young, Son, Boram, Cho, Seong-Woo, Kim, Wantae, Ahn, June Hong, Lee, Wonhwa |
| المصدر: | Proc Natl Acad Sci U S A ; ISSN:1091-6490 ; Volume:121 ; Issue:26 |
| بيانات النشر: | Atypon |
| سنة النشر: | 2024 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | RAGE, TOX, fibroproliferative ARDS, septic shock, severe COVID-19 |
| الوصف: | Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1073/pnas.2319322121Test; https://pubmed.ncbi.nlm.nih.gov/38900789Test |
| DOI: | 10.1073/pnas.2319322121 |
| الإتاحة: | https://doi.org/10.1073/pnas.2319322121Test https://pubmed.ncbi.nlm.nih.gov/38900789Test |
| رقم الانضمام: | edsbas.6F345161 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.2319322121 |
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