Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2001
Tetracyclines inhibit nitrosothiol production by cytokine-stimulated osteoarthritic synovial cells.
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Borderie D, Hernvann A, Hilliquin P, Lemarchal H, Kahan A, Ekindjian O G
Аннотация
OBJECTIVE AND DESIGN: To evaluate the capacity of doxycycline and minocycline to inhibit NO production and N-nitrosation reactions in vitro.
METHODS: Synovial cells obtained from 6 patients with osteoarthritic joint disease were incubated for 24 hours with (i) or without (ii) IL-1beta (1 ng/ml), TNF-alpha (500 pg/ml), IFN-gamma (10(4) U/ml) plus minocycline or doxycycline (10(-4) to 10(-6) M), diclofenac (10(-5) M), or cortisol (10(-5) M). Nitrosothiols were determined by fluorimetry, nitrite by the Griess reaction, nitrate by a spectrophotometric assay using oxidation by nitrate reductase and iNOS by immunoblotting.
RESULTS: After 24 hours of stimulation, the level of NO production was much higher than that in untreated cells: about 5.5 times higher for nitrosothiols, 5.2 times higher for nitrate and about 3.5 times higher for nitrite. Doxycycline and minocycline induced a dose-dependent decrease in the production of nitrosothiols, nitrate and nitrite, and inhibited the synthesis of the iNOS protein. Doxycycline and minocycline inhibited the N-nitrosation reaction of DAN effectively, with IC50 values close to 100 microM. Diclofenac and cortisol had no effect.
CONCLUSION: This study provides new information on the mechanism by which tetracyclines exert anti-inflammatory effects, via inhibiting nitrosothiols.
METHODS: Synovial cells obtained from 6 patients with osteoarthritic joint disease were incubated for 24 hours with (i) or without (ii) IL-1beta (1 ng/ml), TNF-alpha (500 pg/ml), IFN-gamma (10(4) U/ml) plus minocycline or doxycycline (10(-4) to 10(-6) M), diclofenac (10(-5) M), or cortisol (10(-5) M). Nitrosothiols were determined by fluorimetry, nitrite by the Griess reaction, nitrate by a spectrophotometric assay using oxidation by nitrate reductase and iNOS by immunoblotting.
RESULTS: After 24 hours of stimulation, the level of NO production was much higher than that in untreated cells: about 5.5 times higher for nitrosothiols, 5.2 times higher for nitrate and about 3.5 times higher for nitrite. Doxycycline and minocycline induced a dose-dependent decrease in the production of nitrosothiols, nitrate and nitrite, and inhibited the synthesis of the iNOS protein. Doxycycline and minocycline inhibited the N-nitrosation reaction of DAN effectively, with IC50 values close to 100 microM. Diclofenac and cortisol had no effect.
CONCLUSION: This study provides new information on the mechanism by which tetracyclines exert anti-inflammatory effects, via inhibiting nitrosothiols.
Предметные рубрики MeSH
Anti-Bacterial AgentsAnti-Inflammatory AgentsAnti-Inflammatory Agents, Non-SteroidalCell SurvivalCells, CulturedCytokinesDoxycyclineHumansImmunoblottingMinocyclineNitratesNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IINitritesOsteoarthritisOvalbuminS-NitrosothiolsSerine Proteinase InhibitorsSteroidsSynovial MembraneTetracyclines