Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells.
OBJECTIVE
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.
Corps
A N
AN
Rheumatology Research Unit, Box 194, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. anc@mole.bio.cam.ac.uk
Harrall
R L
RL
Curry
V A
VA
Hazleman
B L
BL
Riley
G P
GP
D000125:Achilles Tendon / Q000187:drug effects* / Q000201:enzymology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D017364:Collagenases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D024841:Fluoroquinolones / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D012333:RNA, Messenger; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D020781:Matrix Metalloproteinase 1