title: Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury.
abstract: Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterological Surgery, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterological Surgery, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Fei-Wu
authors.initials: FW
authors.lastname: Long
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Ke-Ling
authors.initials: KL
authors.lastname: Chen
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterological Surgery, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Yang
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Zhao-Yin
authors.initials: ZY
authors.lastname: Lv
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China; and.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Peng
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Oncology, Department of Clinical and Experiment Medicine, Linköping University, Linköping, Sweden.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; liyuanletters@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterological Surgery, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Zong-Guang
authors.initials: ZG
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D015850:Interleukin-6; D016328:NF-kappa B; D020011:Protective Agents; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D002108:Ceruletide; D009195:Peroxidase
keywords: acute pancreatitis; inflammation; lung injury; nuclear factor-κB; resolvin D1