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.