Mediators of Inflammation

Mediators of Inflammation / 2004 / Article

Open Access

Volume 13 |Article ID 478941 |

Ken-Ichi Kanai, Kazuhito Asano, Tadashi Hisamitsu, Harumi Suzaki, "Suppression of matrix metalloproteinase-9 production from neutrophils by a macrolide antibiotic, roxithromycin, in vitro", Mediators of Inflammation, vol. 13, Article ID 478941, 7 pages, 2004.

Suppression of matrix metalloproteinase-9 production from neutrophils by a macrolide antibiotic, roxithromycin, in vitro


BACKGROUND: Macrolide antibiotics such as erythromycin and roxithromycin (RXM) have an anti-inflammatory effect that may account for their clinical benefit in the treatment of chronic airway inflammatory diseases. However, the precise mechanism of this anti-inflammatory effect is not well understood.Purpose: The influence of RXM on matrix metalloproteinase (MMP)-9 production from neutrophils in response to lipopolysaccharide (LPS) stimulation was examined in vitro.Methods: Neutrophils prepared from normal human peripheral blood (1×105 cells/ml) were treated with various concentrations of RXM for 1 h, and then stimulated with 1.0 μg/ml of LPS in the presence of the agent for 24 h. MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels in culture supernatants were examined by enzyme-linked immunosorbent assay.Results: Addition of RXM at more than 5.0 μg/ml into cell cultures caused significant suppression of MMP-9 production, which was increased by LPS stimulation. However, the ability of cells to produce TIMP-1 was not affected by RXM treatment, even when the cells were cultured in the presence of agent at 10.0 μg/ml. We then examined the influence of RXM on transcriptional factor, nuclear factor-κB and activator protein (AP)-1 activation by LPS stimulation. RXM exerted suppressive action on NF-κB (P50 and P65) activation when the cells were cultured for 4 h at more than 5.0 μg/ml of the agent. RXM at more than 2.5 μg/ml also suppressed AP-1 (Fra 1 and Jun B) activation in 4-h cultured cells. We finally examined the influence of RXM on MMP-9 mRNA expression in neutrophils. Addition of RXM into cell cultures at more than 5.0 μg/ml caused significant inhibition of mRNA expression, which was enhanced by LPS stimulation for 12 h.Conclusion: These results strongly suggest that RXM inhibits neutrophil transmigration into inflammatory sites and results in favorable modification of the clinical status of inflammatory diseases.

Copyright © 2004 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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