炎症
受体
生物
未折叠蛋白反应
时尚
细胞生物学
下调和上调
NF-κB
免疫学
细胞凋亡
半胱氨酸蛋白酶
程序性细胞死亡
生物化学
基因
内质网
作者
Graeme P. Sullivan,Hazel O’Connor,Conor M. Henry,P. B. Davidovich,Danielle M. Clancy,Matthew L. Albert,Sean P. Cullen,Séamus J. Martin
标识
DOI:10.1016/j.devcel.2020.01.031
摘要
Inflammation triggered by infection or cellular necrosis is initiated by a battery of pattern-recognition receptors, such as Toll-like receptors or IL-1 family receptors. Diverse forms of cell stress, such as ER stress or mitochondrial stress, can also promote inflammatory responses that contribute to the chronic inflammation observed in cancer, obesity, and other conditions. However, the molecular mechanisms of cell-stress-induced inflammation are poorly understood. Here, we show that ER stress initiated NF-κB activation and inflammation through transcriptional upregulation and ligand-independent activation of TRAIL receptors. ER-stress-induced TRAIL receptor activation resulted in caspase-8/FADD/RIPK1-dependent NF-κB activation and inflammatory cytokine production. Silencing or deletion of TRAIL receptors, or their downstream effectors caspase-8, FADD, or RIPK1, suppressed ER-stress-induced inflammation. Furthermore, chemotherapeutic stress-induced inflammatory responses were blunted in DR5/TRAIL-R null animals. We propose that, upon ER stress, TRAIL receptors serve as “stress-associated molecular patterns (SAMPs)” coupling ER stress to NF-κB-dependent inflammation.
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