PMID- 30055802 OWN - NLM STAT- MEDLINE DCOM- 20190312 LR - 20190312 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 503 IP - 3 DP - 2018 Sep 10 TI - Dihydromyricetin inhibits caerulin-induced TRAF3-p38 signaling activation and acute pancreatitis response. PG - 1696-1702 LID - S0006-291X(18)31603-6 [pii] LID - 10.1016/j.bbrc.2018.07.101 [doi] AB - Acute pancreatitis (AP) is a common inflammatory disease in gastrointestinal tract. Our previous study has shown that caerulin induces TNF receptor-associated factor 3 (TRAF3)-p38 signaling activation and pro-inflammatory response in macrophages, causing damage to co-cultured pancreatic acinar cells. Dihydromyricetin (DHM) is a flavonoid extracted from Ampelopsis grossedentata, which has displayed anti-inflammation and anti-oxidant functions. Our results here show that DHM potently inhibited caerulin-induced expression and productions of multiple pro-inflammatory cytokines (IL-1beta, TNF-alpha and IL-17) in murine bone marrow-derived macrophages (BMDMs). DHM significantly inhibited caerulin-induced TRAF3 protein stabilization, TRAF3-mitogen-activated protein kinase kinase 3 (MKK3) association and following MKK3-p38 activation in BMDMs. Significantly, DHM was ineffective against caerulin in TRAF3-silenced BMDMs. Importantly, DHM supplement attenuated the cytotoxicity of caerulin-activated BMDMs to co-cultured pancreatic acinar cells, resulting in significantly decreased acinar cell death and apoptosis. In vivo, DHM co-administration largely attenuated pancreatic and systemic inflammation in caerulin-injected AP mice. Together, DHM inhibits caerulin-induced TRAF3-p38 signaling activation and AP response. DHM could be further studied as a potential anti-AP agent. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Jia, Rongrong AU - Jia R AD - Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ma, Jiali AU - Ma J AD - Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Meng, Wenying AU - Meng W AD - Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Na AU - Wang N AD - Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: wangnatongren@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180726 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Cytokines) RN - 0 (Flavonols) RN - 0 (TNF Receptor-Associated Factor 3) RN - 888Y08971B (Ceruletide) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - KD8QND6427 (dihydromyricetin) SB - IM MH - Acute Disease MH - Animals MH - Cell Death/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Ceruletide/*antagonists & inhibitors/pharmacology MH - Cytokines/antagonists & inhibitors/biosynthesis MH - Flavonols/*pharmacology MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Pancreatitis/*drug therapy/metabolism/pathology MH - Signal Transduction/*drug effects MH - TNF Receptor-Associated Factor 3/*metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism OTO - NOTNLM OT - Acute pancreatitis OT - Caerulin OT - Dihydromyricetin OT - Pro-inflammatory response OT - TRAF3 EDAT- 2018/07/30 06:00 MHDA- 2019/03/13 06:00 CRDT- 2018/07/30 06:00 PHST- 2018/07/17 00:00 [received] PHST- 2018/07/20 00:00 [accepted] PHST- 2018/07/30 06:00 [pubmed] PHST- 2019/03/13 06:00 [medline] PHST- 2018/07/30 06:00 [entrez] AID - S0006-291X(18)31603-6 [pii] AID - 10.1016/j.bbrc.2018.07.101 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Sep 10;503(3):1696-1702. doi: 10.1016/j.bbrc.2018.07.101. Epub 2018 Jul 26.