Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes.
OBJECTIVE
To determine the in vitro effects of tetracyclines and nonsteroidal antiiflammatory drugs on interleukin 1alpha (IL-1alpha) induced NO production and biosynthesis of inducible NO synthase (iNOS) by articular chondrocytes.


METHODS
Bovine chondrocytes were cultured in alginate beads. Cells were treated with IL-lalpha in the presence or absence of drugs at various concentrations. Expression of mRNA for iNOS was analyzed by reverse transcription polymerase chain reaction-ELISA. Protein synthesis of iNOS was determined by immunoprecipitation. NO production was taken as a measure for the activity of the enzyme.


RESULTS
Minocycline dose dependently reduced IL-1 stimulated NO production by inhibition of the mRNA expression (IC50 = 69.9 microM) and protein synthesis (IC50 = 37.11 microM) of iNOS. Diclofenac-Na at a concentration of 10 microM only weakly reduced nitrite accumulation and mRNA expression of iNOS. No effects were observed for tetracycline, doxycycline, and meloxicam.


CONCLUSIONS
Inhibition of iNOS in articular chondrocytes may be a new mechanism by which minocycline could exert its beneficial effects in the treatment of joint diseases.
Sadowski
T
T
Institute of Pharmacology and Toxicology, University of Bonn, Germany. thorsten.sadowski@biochem.uni-kiel.de
Steinmeyer
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001168:Arthritis / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004008:Diclofenac / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D007596:Joints / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D000077239:Meloxicam; D008911:Minocycline / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D013843:Thiazines; D013844:Thiazoles; D004008:Diclofenac; D019001:Nitric Oxide Synthase; D008911:Minocycline; D000077239:Meloxicam