Related Experiment Video
Updated: Dec 21, 2025
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating
Zengkai Wu1,2, Tunike Mulatibieke3, Mengya Niu1,2
1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
Insights
Matrix metalloproteinase (MMP) inhibition with BB-94 protected against pancreatitis. BB-94 reduced pancreatic inflammation by modulating neutrophil and macrophage activation, decreasing tissue damage and inflammatory mediator expression.
Area of Science:
- Biomedical research
- Inflammation and immunology
- Gastroenterology
Background:
- Acute pancreatitis (AP) involves complex inflammatory responses.
- Matrix metalloproteinases (MMPs) play a role in AP pathogenesis.
- Understanding MMPs' role in immune cell activation is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic potential of MMP inhibition in AP.
- To elucidate the role of MMPs in neutrophil and macrophage activation during pancreatitis.
- To assess the effects of BB-94 on inflammatory mediators and NF-κB activation.
Main Methods:
- Acute pancreatitis was induced in Balb/C mice using caerulein and LPS.
- Mice were treated with the MMP inhibitor BB-94.
- Histology, serum amylase/lipase, cytokine/chemokine expression, and NF-κB activation were assessed. Isolated neutrophils and macrophages were used to evaluate cellular responses.
Main Results:
- MMP-9 was upregulated in caerulein-induced pancreatitis.
- BB-94 treatment ameliorated pancreatic tissue damage and reduced inflammatory mediator expression (TNFα, IL-6, CCL2, CXCL2).
- BB-94 inhibited neutrophil reactive oxygen species (ROS) production, inflammatory macrophage polarization, and NF-κB activation.
Conclusions:
- MMP inhibition with BB-94 demonstrates a protective effect against pancreatic inflammation in AP.
- BB-94 exerts its protective effects by modulating neutrophil and macrophage activation pathways.
- Targeting MMPs represents a promising therapeutic strategy for managing acute pancreatitis.
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