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Rheumatology Advance Access published online on September 7, 2005
Rheumatology, doi:10.1093/rheumatology/kei087
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 1, 2005
Accepted August 1, 2005

Original Papers

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

A. N. Corps 1*, R. L. Harrall 1, V. A. Curry 1, B. L. Hazleman 1, and G. P. Riley 1

1 Rheumatology Research Unit, Box 194, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.

* To whom correspondence should be addressed.
A. N. Corps, E-mail: anc{at}mole.bio.cam.ac.uk


  Abstract

Objectives. Fluoroquinolone antibiotics may cause tendon pain and rupture. We reported previously that the fluoroquinolone ciprofloxacin potentiated interleukin (IL)-1{beta}-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-1{beta}. 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-1{beta}. Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA. In contrast, ciprofloxacin and norfloxacin increased basal and IL-1{beta}-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-1{beta}-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.

Keywords: Collagenase; Fluoroquinolone; Interleukin; Matrix metalloproteinase; Tendon.
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