TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model
Acute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00980/full |
| _version_ | 1811266121633890304 |
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| author | Chaohao Huang Chaohao Huang Chaohao Huang Shengchuan Chen Shengchuan Chen Shengchuan Chen Tan Zhang Tan Zhang Tan Zhang Dapei Li Dapei Li Zhonglin Huang Zhonglin Huang Jian Huang Yanghua Qin Bicheng Chen Genhong Cheng Genhong Cheng Feng Ma Feng Ma Feng Ma Mengtao Zhou |
| author_facet | Chaohao Huang Chaohao Huang Chaohao Huang Shengchuan Chen Shengchuan Chen Shengchuan Chen Tan Zhang Tan Zhang Tan Zhang Dapei Li Dapei Li Zhonglin Huang Zhonglin Huang Jian Huang Yanghua Qin Bicheng Chen Genhong Cheng Genhong Cheng Feng Ma Feng Ma Feng Ma Mengtao Zhou |
| author_sort | Chaohao Huang |
| collection | DOAJ |
| description | Acute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll-like receptor 3 (TLR3) ligand polyI:C is a double-stranded RNA mimic that can be used as an immune stimulant. Our current study indicates that polyI:C exerted excellent anti-inflammatory effects in a caerulein-induced AP mouse model and taurocholate-induced pancreatic acinar cell line injury model. We found that polyI:C triggers type I interferon (IFN) production and downstream IFN-α/β receptor (IFNAR)-dependent signaling, which play key roles in protecting the pancreas from inflammatory injury. Knockout of IFN-β and IFNAR in mice abolished the preventive effects of polyI:C on caerulein-induced AP symptoms, which include pancreatic edema, neutrophil infiltration, the accumulation of reactive oxygen species (ROS), and inflammatory gene expression. Treating pancreatic acinar 266-6 cells with an IFNAR inhibitor, which blocks the interaction between type I IFN and IFNAR, diminishes the downregulation of oxidative stress by polyI:C. Additionally, a subsequent transcriptome analysis on the role of polyI:C in treating pancreatitis suggested that chemotaxis of neutrophils and the production of ROS were inhibited by polyI:C in the pancreases damaged by caerulein injection. Thus, polyI:C may act as a type I IFN inducer to alleviate AP, and it has the potential to be a promising therapeutic agent used at the early stages of AP. |
| first_indexed | 2024-04-12T20:36:22Z |
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| id | doaj.art-b5f84c1be01147a9bb340b97a773f461 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T20:36:22Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-b5f84c1be01147a9bb340b97a773f4612022-12-22T03:17:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.00980432189TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse ModelChaohao Huang0Chaohao Huang1Chaohao Huang2Shengchuan Chen3Shengchuan Chen4Shengchuan Chen5Tan Zhang6Tan Zhang7Tan Zhang8Dapei Li9Dapei Li10Zhonglin Huang11Zhonglin Huang12Jian Huang13Yanghua Qin14Bicheng Chen15Genhong Cheng16Genhong Cheng17Feng Ma18Feng Ma19Feng Ma20Mengtao Zhou21Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Emergency, First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Laboratory Diagnosis, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSuzhou Institute of Systems Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaAcute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll-like receptor 3 (TLR3) ligand polyI:C is a double-stranded RNA mimic that can be used as an immune stimulant. Our current study indicates that polyI:C exerted excellent anti-inflammatory effects in a caerulein-induced AP mouse model and taurocholate-induced pancreatic acinar cell line injury model. We found that polyI:C triggers type I interferon (IFN) production and downstream IFN-α/β receptor (IFNAR)-dependent signaling, which play key roles in protecting the pancreas from inflammatory injury. Knockout of IFN-β and IFNAR in mice abolished the preventive effects of polyI:C on caerulein-induced AP symptoms, which include pancreatic edema, neutrophil infiltration, the accumulation of reactive oxygen species (ROS), and inflammatory gene expression. Treating pancreatic acinar 266-6 cells with an IFNAR inhibitor, which blocks the interaction between type I IFN and IFNAR, diminishes the downregulation of oxidative stress by polyI:C. Additionally, a subsequent transcriptome analysis on the role of polyI:C in treating pancreatitis suggested that chemotaxis of neutrophils and the production of ROS were inhibited by polyI:C in the pancreases damaged by caerulein injection. Thus, polyI:C may act as a type I IFN inducer to alleviate AP, and it has the potential to be a promising therapeutic agent used at the early stages of AP.https://www.frontiersin.org/article/10.3389/fimmu.2019.00980/fullacute pancreatitisTLR3 ligandspolyI:Creactive oxygen speciestype I interferonIFN-β |
| spellingShingle | Chaohao Huang Chaohao Huang Chaohao Huang Shengchuan Chen Shengchuan Chen Shengchuan Chen Tan Zhang Tan Zhang Tan Zhang Dapei Li Dapei Li Zhonglin Huang Zhonglin Huang Jian Huang Yanghua Qin Bicheng Chen Genhong Cheng Genhong Cheng Feng Ma Feng Ma Feng Ma Mengtao Zhou TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model Frontiers in Immunology acute pancreatitis TLR3 ligands polyI:C reactive oxygen species type I interferon IFN-β |
| title | TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model |
| title_full | TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model |
| title_fullStr | TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model |
| title_full_unstemmed | TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model |
| title_short | TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-β/Interferon-α/β Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model |
| title_sort | tlr3 ligand polyi c prevents acute pancreatitis through the interferon β interferon α β receptor signaling pathway in a caerulein induced pancreatitis mouse model |
| topic | acute pancreatitis TLR3 ligands polyI:C reactive oxygen species type I interferon IFN-β |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00980/full |
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