AI Article Synopsis
- Matrix metalloproteinases (MMPs), specifically MMP-1, are crucial for breaking down the extracellular matrix and are involved in tissue remodeling.
- The study explored how human pancreatic periacinar myofibroblasts secrete MMP-1 in response to pro-inflammatory cytokines IL-1beta and TNF-alpha, discovering that cytokine stimulation occurs in a dose- and time-dependent manner.
- It was found that the secretion mostly consisted of inactive pro-MMP-1, and the process was regulated mainly through the MEK/ERK signaling pathway, indicating the significant role of myofibroblasts in chronic pancreatitis tissue remodeling.
Article Abstract
Matrix metalloproteinases (MMPs) are the proteases involved in the degradation of the extracellular matrix. MMP-1 is thought to be one of the key enzymes in fibrolysis, a process closely related to tissue remodeling. In the present study, we investigated MMP-1 secretion from human pancreatic periacinar myofibroblasts in response to pro-inflammatory cytokines IL-1beta and TNF-alpha. We also attempted to clarify the intracellular signaling pathways mediating the cytokine-induced MMP-1 secretion. MMP-1 secretion was measured by an enzyme-linked immunosorbent assay. MMP-1 molecules were analyzed by Western blotting. MMP-1 mRNA expression was evaluated by Northern blotting. IL-1l and TNF-alpha stimulated the MMP-1 secretion in a dose- and time-dependent manner. Ninety percent of MMP-1 was secreted as inactive form (pro-MMP-1). The effects of IL-1beta and TNF-alpha were significantly inhibited by PD98059 MEK/ERK inhibitor). In contrast, SB203580 (p38 MAPK inhibitor), GF109203X (PKC inhibitor), and PDTC (NF-kappaB inhibitor) did not alter the MMP-1 secretion induced by IL-1beta and TNF-alpha. These effects were also observed at them RNA level. In conclusion, in human pancreatic periacinar myofibroblasts, MMP-1 secretion was regulated by the pro-inflammatory cytokines via the MEK/ERK cascade. Thus, human pancreatic periacinar myofibroblasts may play an important role in the remodeling of damaged pancreatic tissue in chronic pancreatitis via MMP-1 secretion.
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| http://dx.doi.org/10.1159/000073889 | DOI Listing |
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