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Corps, A.N. et al.

Corps, Harrall, Curry, Hazleman, Riley,

Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells.

OBJECTIVES: Fluoroquinolone antibiotics may cause tendon pain and rupture. We reported previously that the fluoroquinolone ciprofloxacin potentiated interleukin (IL)-1beta-stimulated expression of matrix metalloproteinases (MMP)-3 and MMP-1 in human tendon-derived cells. We have now tested additional fluoroquinolones and investigated whether they have a similar effect on expression of MMP-13. METHODS: Tendon cells were incubated for two periods of 48 h with or without fluoroquinolones and IL-1beta. Total ribonucleic acid (RNA) was assayed for MMP messenger RNA by relative quantitative reverse transcriptase polymerase chain reaction, with normalization for glyceraldehyde-3-phosphate dehydrogenase mRNA. Samples of supernatant medium were assayed for MMP output by activity assays. RESULTS: MMP-13 was expressed by tendon cells at lower levels than MMP-1, and was stimulated typically 10- to 100-fold by IL-1beta. Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA. In contrast, ciprofloxacin and norfloxacin increased basal and IL-1beta-stimulated MMP-1 mRNA expression. Both the inhibition of MMP-13 and the potentiation of MMP-1 expression by fluoroquinolones were accompanied by corresponding changes in IL-1beta-stimulated MMP output. The non-fluorinated quinolone nalidixic acid had lesser or no effects. CONCLUSIONS: Fluoroquinolones show contrasting effects on the expression of the two collagenases MMP-1 and MMP-13, indicating specific effects on MMP gene regulation.[1]

References

Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells. Corps, A.N., Harrall, R.L., Curry, V.A., Hazleman, B.L., Riley, G.P. Rheumatology (Oxford, England) (2005) [Pubmed]

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