Modulation of nitric oxide production by tetracyclines and chemically modified tetracyclines.
Chemically modified tetracyclines (CMTs) dose-dependently decreased inducible nitric oxide synthase (iNOS) and, consequently, nitric oxide (NO) formation by the lipopolysaccharide (LPS)-stimulated J774 line. The inhibitory effect was due to a specific reduction in the iNOS protein content in the cells, as attested by Western blot analysis and by the inhibition of iNOS mRNA accumulation. Furthermore, CMTs cause a dose-dependent increase in cell death in the J774 line mediated by the NO-independent apoptotic mechanism.
Cillari
E
E
Institute of General Pathology, University of Palermo, Italy.
Milano
S
S
D'Agostino
P
P
Di Bella
G
G
La Rosa
M
M
Barbera
C
C
Ferlazzo
V
V
Cammarata
G
G
Grimaudo
S
S
Tolomeo
M
M
Feo
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013754:Tetracyclines / Q000737:chemistry / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology