Matrix metalloproteinase-3 secretion from human pancreatic periacinar myofibroblasts in response to inflammatory mediators
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Updated: Jul 18, 2026

Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Osamu Inatomi1, Akira Andoh, Yuhki Yagi
1Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Objectives:
Matrix metalloproteinases (MMPs) play roles in the pathophysiology of pancreatic disorders. However, the regulation of MMP-3 secretion in the pancreas remains unclear. In this study, we assessed the expression of MMP-3 in human pancreatic periacinar myofibroblasts.
Methods:
MMP-3 secretion and MMP-3 mRNA expression were determined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively.
Results:
In human pancreatic myofibroblasts, MMP-3 secretion and mRNA expression were induced by interleukin (IL)-17, IL-1beta, and tumor necrosis factor (TNF) -alpha, respectively. The effects of IL-17 were detected as similar in extent to those induced by IL-1beta or TNF-alpha. Costimulation by IL-17 plus IL-1beta and/or IL-17 plus TNF-alpha induced a synergistic increase in MMP-3 secretion, although the costimulatory effects of these combinations were not detected in tissue inhibitor of matrix metalloproteinase-1 secretion. Adenovirus-mediated transfer of a stable form of IkappaBalpha markedly inhibited the effects of IL-17, IL-1beta, and TNF-alpha. Mitogen-activated protein kinase inhibitors (U0126, PD098059, and SB203580) also blocked MMP-3 secretion. These findings indicate a role for nuclear factor-kappaB and mitogen-activated protein kinases in cytokine-induced MMP-3 secretion.
Conclusions:
Pancreatic periacinar myofibroblasts actively secrete MMP-3 in response to IL-17, IL-1beta, and TNF-alpha. Pancreatic myofibroblasts may play an important role in extracellular matrix turnover via MMP-3 secretion in the pancreas.
Insights
Human pancreatic myofibroblasts secrete matrix metalloproteinase-3 (MMP-3) when stimulated by inflammatory cytokines IL-17, IL-1beta, and TNF-alpha. This suggests a role for these cells in pancreatic tissue remodeling.
Area of Science:
- Cell Biology
- Biochemistry
- Gastroenterology
Background:
- Matrix metalloproteinases (MMPs) are implicated in pancreatic disorders.
- The specific regulation of MMP-3 secretion in the pancreas is not well understood.
Purpose of the Study:
- To investigate the expression and regulation of MMP-3 in human pancreatic periacinar myofibroblasts.
Main Methods:
- MMP-3 secretion was measured using enzyme-linked immunosorbent assay.
- MMP-3 mRNA expression was quantified by real-time polymerase chain reaction.
- The roles of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) were assessed using specific inhibitors and gene transfer.
Main Results:
- Interleukin-17 (IL-17), IL-1beta, and tumor necrosis factor-alpha (TNF-α) significantly induced MMP-3 secretion and mRNA expression in pancreatic myofibroblasts.
- Synergistic increases in MMP-3 secretion were observed with combined cytokine stimulation (IL-17 + IL-1beta or IL-17 + TNF-α).
- Inhibition of NF-κB and MAPKs pathways blocked cytokine-induced MMP-3 secretion, indicating their crucial roles.
Conclusions:
- Pancreatic periacinar myofibroblasts actively secrete MMP-3 in response to key inflammatory cytokines.
- These cells may contribute to extracellular matrix turnover in the pancreas through MMP-3 secretion.
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