ReferenceID 1814

Ellipticine blocks synergistic effects of IL-17A and TNF-α in epithelial cells and alleviates severe acute pancreatitis-associated acute lung injury

Biochem Pharmacol

IL-17A combined with TNF-alpha plays a vital role in inflammatory response and interference of the synergistic effect is an effective strategy for treating inflammatory diseases. Ellipticine, a natural alkaloid, has biol

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Reference Id
1814
Evidence Id
18404
Core Evidence Id
18404
Source Reference Id
3614
Herb2 Reference Id
HBREF004411
Subject Paper Key
HBIN025012_32335141
Pubmed Id
32335141
Doi
10.1016/j.bcp.2020.113992
Paper Title
Ellipticine blocks synergistic effects of IL-17A and TNF-α in epithelial cells and alleviates severe acute pancreatitis-associated acute lung injury
Paper Abstract
IL-17A combined with TNF-alpha plays a vital role in inflammatory response and interference of the synergistic effect is an effective strategy for treating inflammatory diseases. Ellipticine, a natural alkaloid, has biological activities on anti-tumor and anti-HIV. However, it is still unknown whether ellipticine can inhibit IL-17A and TNF-alpha-mediated signaling and has treatment effect on PALI. Here, we reported that ellipticine significantly inhibited the production of pro-inflammatory cytokines and chemokines in pulmonary epithelial cell BEAS-2B treated with IL-17A and TNF-alpha, but not IL-17A or TNF-alpha alone. Meanwhile, ellipticine attenuated NF-kappaB and MAPKs activation in response to IL-17A and TNF-alpha treatment, inhibited Act1 and TRAF6-mediated NF-kappaB activation, and blocked the interaction of Act1 with TRAF6. Furthermore, we found that ellipticine significantly alleviated CAE and LPS-induced SAP/PALI. Ellipticine treatment dramatically reduced inflammatory cells infiltration, MPO activity, serum amylase and lipase activity and the protein concentration of BALF. Collectively, our findings indicate that ellipticine inhibits the synergistic effect of IL-17A and TNF-alpha by targeting on Act1 and TRAF6 interaction and is a potential therapeutic agent for the treatment of SAP/PALI.
Journal
Biochem Pharmacol
Publish Year
2020
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Inflammatory Diseases
Paper Title Cn
Paper Title En
Ellipticine blocks synergistic effects of IL-17A and TNF-α in epithelial cells and alleviates severe acute pancreatitis-associated acute lung injury
Bilingual Status
semi_complete