Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts: role of interleukin-17.
BACKGROUND
Subepithelial myofibroblasts (SEMFs) play a role in extracellular matrix (ECM) metabolism in the colon. In this study, we investigated the effects of interleukin (IL)-17, IL-1beta, and tumor necrosis factor (TNF)-alpha on matrix metalloproteinase (MMP)-3 secretion in colonic SEMFs.


METHODS
MMP-3 secretion and MMP-3 mRNA expression were determined by Western and Northern blotting, respectively. The secretion of tissue inhibitor of matrix metalloproteinase (TIMP)-1 was determined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
In human colonic SEMFs, MMP-3 secretion and MMP-3 mRNA expression were induced by IL-17, IL-1beta, and TNF-alpha. The effect of IL-17 was observed, but this was weak as compared with those induced by IL-1beta or TNF-alpha. A c-Jun/activating protein-1 (AP-1) inhibitor, curcumin, reduced the IL-17-, IL-1beta-, and TNF-alpha-induced MMP-3 mRNA expression, and mitogen-activated protein (MAP) kinase inhibitors (U0126, PD098059, and SB203580) also blocked MMP-3 secretion. There findings indicate a role for AP-1 and MAP kinases in cytokine-induced MMP-3 secretion. Furthermore, costimulation by IL-17 + IL-1beta and by IL-17 + TNF-alpha induced a marked increase in MMP-3 secretion. The costimulatory effects of these combinations were also observed for TIMP-1 mRNA expression and TIMP-1 secretion.


CONCLUSIONS
Colonic SEMFs actively secreted MMP-3 in response to IL-17, IL-1beta, and TNF-alpha. This was coupled with TIMP-1 secretion. Colonic SEMFs may play an important role in ECM turnover via MMP secretion.
Bamba
Shigeki
S
Division of Gastroenterology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Japan.
Andoh
Akira
A
Yasui
Hirofumi
H
Araki
Yoshio
Y
Bamba
Tadao
T
Fujiyama
Yoshihide
Y
D015152:Blotting, Northern; D015153:Blotting, Western; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D020381:Interleukin-17; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D019278:Matrix Metalloproteinase 3