Inhibitory effects of short-chain fatty acids on matrix metalloproteinase secretion from human colonic subepithelial myofibroblasts.
OBJECTIVE
Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are the major by-product of bacterial fermentation of dietary fiber in the colon. In this report, we investigated how SCFAs modulate matrix metalloproteinase (MMP) secretion from human colonic subepithelial myofibroblasts (SEMFs).


METHODS
SEMFs were identified by expression of alpha-smooth muscle actin and vimentin. Cytokine-induced MMP-1 and MMP-3 levels were determined by enzyme-linked immunosorbent assay. Cytokine-induced MMP mRNA expression was analyzed by RT-PCR and real-time PCR methods.


RESULTS
Acetate had no effect on MMP secretion. Propionate and butyrate significantly attenuated IL-1 beta- and TNF-alpha-induced MMP-1 and MMP-3 secretion. Similar responses were also observed at the mRNA levels. Propionate and butyrate did not modulate IL-1 beta- and TNF-alpha-induced activation of mitogen-activated protein kinases (MAPKs), which play a crucial role in MMP induction. Trichostatin A, a histone-deacetylase inhibitor, reduced IL-1 beta-induced MMP-1 and MMP-3 mRNA expression, and suppressed TNF-alpha-induced MMP-3 mRNA expression.


CONCLUSIONS
SCFAs play an anti-inflammatory role through suppression of MMP secretion in the colon. Inhibitory effects of SCFAs on MMP secretion might be associated with their action of histone hyperacetylation.
Kawamura
Takato
T
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, 520-2192, Japan.
Andoh
Akira
A
Nishida
Atsushi
A
Shioya
Makoto
M
Yagi
Yuhki
Y
Nishimura
Takashi
T
Hashimoto
Takayoshi
T
Tsujikawa
Tomoyuki
T
Yasui
Hiroyuki
H
Fujiyama
Yoshihide
Y
D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D005232:Fatty Acids, Volatile / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids; D053583:Interleukin-1beta / Q000502:physiology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D005232:Fatty Acids, Volatile; D006877:Hydroxamic Acids; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D020928:Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1