Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation
Joint Authors
Wen, Li
Wu, Zengkai
Mulatibieke, Tunike
Niu, Mengya
Li, Bin
Dai, Juanjuan
Ye, Xin
He, Yan
Chen, Congying
Hu, Guoyong
Source
Gastroenterology Research and Practice
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-28
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Background/Objective.
Inhibition of matrix metalloproteinases (MMPs), particularly MMP-9, attenuates leukocyte infiltration and pancreatic and distant organ damages in acute pancreatitis (AP).
However, it is unclear whether MMPs mediate inflammatory cell activation.
In this study, we investigated the effects of inhibition of MMPs on neutrophil and macrophage activation in caerulein-induced pancreatitis.
Methods.
AP was induced in Balb/C mice by ten hourly intraperitoneal injections of caerulein (100 μg/kg) and LPS (5 mg/kg).
The MMP inhibitor, BB-94 (20 mg/kg) was intraperitoneally administered 30 min before AP induction.
Pancreatitis was confirmed by histology and serum amylase and lipase.
Expression of pancreatic proinflammatory mediators and NF-κB activation were assessed.
Bone marrow-derived neutrophils (BMDNs) and macrophages (BMDMs) were isolated.
BMDNs were activated by phorbol 12-myristate 13-acetate (PMA, 50 ng/ml) and neutrophil reactive oxygen species (ROS) production was recorded.
BMDMs were stimulated with 10 ng/ml IFN-γ and 100 ng/ml LPS to induce M1 macrophage polarization.
Results.
Pancreatic MMP-9 was markedly upregulated and serum MMP-9 was increased in caerulein-induced pancreatitis.
Inhibition of MMP with BB-94 ameliorated pancreatic tissue damage and decreased the expression of proinflammatory cytokines (TNFα and IL-6) or chemokines (CCL2 and CXCL2) and NF-κB activation.
Furthermore, using isolated BMDNs and BMDMs, we found that inhibition of MMP with BB-94 markedly decreased neutrophil ROS production, inhibited inflammatory macrophage polarization and NF-κB activation.
Conclusions.
Our results showed that inhibition of MMP with BB-94 protected against pancreatic inflammatory responses in caerulein-induced pancreatitis via modulating neutrophil and macrophage activation.
American Psychological Association (APA)
Wu, Zengkai& Mulatibieke, Tunike& Niu, Mengya& Li, Bin& Dai, Juanjuan& Ye, Xin…[et al.]. 2020. Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation. Gastroenterology Research and Practice،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1167091
Modern Language Association (MLA)
Wu, Zengkai…[et al.]. Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation. Gastroenterology Research and Practice No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1167091
American Medical Association (AMA)
Wu, Zengkai& Mulatibieke, Tunike& Niu, Mengya& Li, Bin& Dai, Juanjuan& Ye, Xin…[et al.]. Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation. Gastroenterology Research and Practice. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1167091
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1167091