Matrix metalloproteinase-3 secretion from human pancreatic periacinar myofibroblasts in response to inflammatory

Osamu Inatomi1, Akira Andoh, Yuhki Yagi

  • 1Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.

Pancreas
|January 2, 2007
PubMed
Abstract

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.

Related Concept Videos

Acute Pancreatitis II: Pathophysiology01:21

Acute Pancreatitis II: Pathophysiology

The pathophysiology of acute pancreatitis centers on injury to pancreatic acinar cells, which initiates a cascade of harmful intracellular events.This injury leads to premature activation of trypsinogen to trypsin in the pancreas. Trypsin then activates other digestive enzymes, such as chymotrypsin, elastase, and phospholipase A2, which begin breaking down pancreatic tissue. The resulting autodigestion causes local inflammation, tissue swelling, hemorrhage, and fat necrosis.Injured acinar cells...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Chronic Pancreatitis I: Introduction01:24

Chronic Pancreatitis I: Introduction

The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
Acute Pancreatitis I: Introduction01:27

Acute Pancreatitis I: Introduction

Pancreatitis is inflammation of the pancreas, an organ located behind the stomach. It can be either acute or chronic.
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include:
Acute Pancreatitis I: Introduction01:25

Acute Pancreatitis I: Introduction

Acute pancreatitis is the sudden inflammation of the pancreas caused by the early activation of digestive enzymes, leading to the autodigestion of pancreatic tissue. This results in local inflammation and, in severe cases, systemic complications.EtiologyUnderstanding the underlying causes is crucial, as identifying the etiology guides treatment and anticipates complications. Acute pancreatitis can be triggered by various factors, typically grouped into the following clinical categories.Biliary...
Acute Inflammation I: Inflammatory Response01:26

Acute Inflammation I: Inflammatory Response

Acute inflammation is a rapid, short-lived physiological response to tissue injury or infection, designed to eliminate harmful agents and initiate repair. This tightly regulated process typically lasts from minutes to several days and is triggered by factors such as microbial invasion, physical trauma, or chemical injury.Recognition and Mediator ReleaseThe inflammatory response begins when resident immune cells—such as mast cells, macrophages, and dendritic cells—detect damage-associated...