Rheumatology Advance Access originally published online on September 7, 2005
Rheumatology 2005 44(12):1514-1517; doi:10.1093/rheumatology/kei087
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Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells
Rheumatology Research Unit, Box 194, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Correspondence to: A. N. Corps, Rheumatology Research Unit, Box 194, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. E-mail: anc{at}mole.bio.cam.ac.uk
Objectives. Fluoroquinolone antibiotics may cause tendon pain and rupture. We reported previously that the fluoroquinolone ciprofloxacin potentiated interleukin (IL)-1ß-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-1ß. 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-1ß. Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA. In contrast, ciprofloxacin and norfloxacin increased basal and IL-1ß-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-1ß-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.
KEY WORDS: Collagenase, Fluoroquinolone, Interleukin, Matrix metalloproteinase, Tendon
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