Effect of erythromycin on matrix metalloproteinase-9 and cell migration.
Erythromycin (EM) has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To investigate the mechanism of this anti-inflammatory effect, we studied the relationship between the concentration of EM and matrix metalloproteinase-9 (MMP-9) activity, which is important in cell migration. We showed that EM suppressed the gelatinolytic activity of U937 cell-derived MMP-9 by using gelatin zymography, showed that expressions of MMP-9 protein and MMP-9 mRNA were down-regulated by EM in a dose-dependent manner, and showed that U937 migration was also suppressed by EM. We also demonstrated that EM treatment suppressed the gelatinolytic activity of MMP-9 in spleen macrophages. These findings suggest that the suppressive effect of EM on MMP-9 activity is one of the anti-inflammatory mechanisms that inhibit the migration of inflammatory cells into the inflammatory site.
First Department of Internal Medicine, Department of Clinical Preventive Medicine, Nagoya University School of Medicine, Japan.
N
N
Hashimoto
T
T
Kawabe
T
T
Hara
K
K
Imaizumi
H
H
Wakayama
H
H
Saito
K
K
Shimokata
Y
Y
Hasegawa
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D020298:U937 Cells
D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D004917:Erythromycin; D020780:Matrix Metalloproteinase 9