دورية أكاديمية
Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury
| العنوان: | Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury |
|---|---|
| المؤلفون: | Sabyasachi Bhattacharya, Kanstantsin V Katlinski, Maximilian Reichert, Shigetsugu Takano, Angela Brice, Bin Zhao, Qiujing Yu, Hui Zheng, Christopher J Carbone, Yuliya V Katlinskaya, N Adrian Leu, Kelly A McCorkell, Satish Srinivasan, Melanie Girondo, Hallgeir Rui, Michael J May, Narayan G Avadhani, Anil K Rustgi, Serge Y Fuchs |
| المصدر: | EMBO Molecular Medicine, Vol 6, Iss 3, Pp 384-397 (2014) |
| بيانات النشر: | Springer Nature, 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | hepatitis, inflammation, interferon, pancreatitis, receptor, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1SA knock‐in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1SA mice (or their bone marrow‐receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1SA mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation‐induced tissue damage can be purposely mimicked for therapeutic benefits. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.1002/emmm.201303236 |
| URL الوصول: | https://doaj.org/article/023f6fcb1025437991143748532942e5 |
| رقم الأكسشن: | edsdoj.023f6fcb1025437991143748532942e5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
|---|---|
| DOI: | 10.1002/emmm.201303236 |