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. 2004 Dec;13(5-6):313–319. doi: 10.1155/S0962935104000468

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

Ken-Ichi Kanai 1, Kazuhito Asano 1, Tadashi Hisamitsu 1, Harumi Suzaki 1
PMCID: PMC1781582  PMID: 15770046

Abstract

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 x 10(5) cells/ml) were treated with various concentrations of RXM for 1 h, and then stimulated with 1.0 microg/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 microg/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 microg/mL We then examined the influence of RXM on transcriptional factor, nuclear factor-kappaB and activator protein (AP)-1 activation by LPS stimulation. RXM exerted suppressive action on NF-kappaB (P50 and P65) activation when the cells were cultured for 4 h at more than 5.0 microg/ml of the agent. RXM at more than 2.5 microg/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 microg/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.

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Selected References

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