التفاصيل البيبلوغرافية
| العنوان: |
Macrophage RIPK3 triggers inflammation and cell death via the XBP1-Foxo1 axis in liver ischaemia-reperfusion injury. |
| المؤلفون: |
Qu, Xiaoye, Yang, Tao, Wang, Xiao, Xu, Dongwei, Yu, Yeping, Li, Jun, Jiang, Longfeng, Xia, Qiang, Farmer, Douglas, Ke, Bibo |
| المصدر: |
JHEP Reports, vol 5, iss 11 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2023 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
ER stress, Foxo1, IRE1α, Innate immunity, Liver inflammation, Necroptosis, Reactive oxygen species, XBP1 |
| الوصف: |
BACKGROUND & AIMS: Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) is a central player in triggering necroptotic cell death. However, whether macrophage RIPK3 may regulate NOD1-dependent inflammation and calcineurin/transient receptor potential cation channel subfamily M member 7 (TRPM7)-induced hepatocyte death in oxidative stress-induced liver inflammatory injury remains elusive. METHODS: A mouse model of hepatic ischaemia-reperfusion (IR) injury, the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific RIPK3 knockout (RIPK3M-KO) and RIPK3-proficient (RIPK3FL/FL) mice. RESULTS: RIPK3M-KO diminished IR stress-induced liver damage with reduced serum alanine aminotransferase/aspartate aminotransferase levels, macrophage/neutrophil infiltration, and pro-inflammatory mediators compared with the RIPK3FL/FL controls. IR stress activated RIPK3, inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α), x-box binding protein 1 (XBP1), nucleotide-binding oligomerisation domain-containing protein 1 (NOD1), NF-κB, forkhead box O1 (Foxo1), calcineurin A, and TRPM7 in ischaemic livers. Conversely, RIPK3M-KO depressed IRE1α, XBP1, NOD1, calcineurin A, and TRPM7 activation with reduced serum tumour necrosis factor α (TNF-α) levels. Moreover, Foxo1M-KO alleviated IR-induced liver injury with reduced NOD1 and TRPM7 expression. Interestingly, chromatin immunoprecipitation coupled with massively parallel sequencing revealed that macrophage Foxo1 colocalised with XBP1 and activated its target gene Zc3h15 (zinc finger CCCH domain-containing protein 15). Activating macrophage XBP1 enhanced Zc3h15, NOD1, and NF-κB activity. However, disruption of macrophage Zc3h15 inhibited NOD1 and hepatocyte calcineurin/TRPM7 activation, with reduced reactive oxygen species production and lactate dehydrogenase release after macrophage/hepatocyte coculture. Furthermore, adoptive transfer of Zc3h15-expressing macrophages in RIPK3M-KO mice augmented IR-triggered liver inflammation and ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt3tb8w9mx; https://escholarship.org/uc/item/3tb8w9mxTest |
| الإتاحة: |
https://escholarship.org/uc/item/3tb8w9mxTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.B621318D |
| قاعدة البيانات: |
BASE |
