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.
inducible nitric oxide synthase mRNA in murine macrophages by doxycycline and chemically modified tetracyclines. FEBS Lett410:259-264.
2.
D'Agostino P., La Rosa M., Barbera C., Arcoleo F., Di Bella G., Milano S., et al. (1998a). Doxycycline reduces mortality to lethal endotoxemia by reducing nitric oxide synthesis via an interleukin-10-independent mechanism. J Infect Dis177:489-492.
3.
D'Agostino P., Arcoleo F., Barbera C., Di Bella G., La Rosa M., Misiano G., et al. (1998b). Tetracyclines inhibit the nitric oxide synthases activity induced by endotoxin in cultured murine macrophages. Eur J Pharmacol346:283-290.
4.
Darzynkiewicz Z., Bruno S., Del Bino G., Gorczyca W., Holz MA, Lassota P., et al. (1992). Features of apoptotic cells measured by flow cytometry. Cytometry13:795-808.
5.
Duke RC, Cohen JJ (1992). Morphological and biochemical assays of apoptosis . In: Current protocols in immunology. Coligan JE, Kruisbeak AM, editors. New York: J. Wiley & Sons, pp. 3.17.1-3.17.16.
6.
ElAttar Tma, Lin HS, Schultz RJ (1988). Effect of minocycline on prostaglandin formation in gingival fibroblast. J Periodont Res23:285-286.
7.
Gabler WL, Creamer HR (1991). Suppression of human neutrophil functions by tetracyclines . J Periodont Res26:52-58.
8.
Giallongo A., Feo S., Moore R., Croce CM, Showe LC (1986). Molecular cloning and nucleotide sequence of a full-length cDNA for human a enolase. Proc Natl Acad Sci USA83:6741-6745.
9.
Golub LM, Ramamurthy NS, McNamara TF, Gomes B., Wolff M., Casino A., et al. (1984). Tetracyclines inhibit tissue collagenase activity: a new mechanism for treatment of periodontal disease. J Periodont Res19:651-655.
10.
Golub LM, Suomalainen K., Sorsa T. (1992). Host modulation with tetracyclines and their chemically modified analogues. Curr Opin Dent2:80-90.
11.
Hoffman B., Liebermann DA (1994). Molecular controls of apoptosis: differentiation/growth arrest primary response genes, proto-oncogenes, and tumor suppressor genes as positive & negative modulators. Oncogene9:1807-1812.
12.
lalenti A., lanaro A., Moncada S., Di Rosa M. (1992). Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol211:177-182.
13.
Laemmli UK (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680-685.
14.
Milano S., Arcoleo F., D'Agostino P., Cillari E. (1997). Intraperitoneal injection of tetracyclines protect mice from lethal endotoxemia down-regulating inducible nitric oxide synthase in various organs and cytokines and nitrate secretion in the blood. Antimicrob Agents Chemother41:117-121.
15.
Mosmann TJ (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Meth65:55-61.
16.
Salter M., Knowles RG, Moncada S. (1991). Widespread tissue distribution, species distribution and changes in activity of Ca2+-dependent and Ca2+-independent nitric oxide synthase. FEBS Lett291:145-153.
17.
Thomsen LL, Scott Jmj, Topley P., Knowles RG, Keerie AJ, Frend AJ (1997). Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor . Cancer Res57:3300-3304.
18.
Vadas P., Greenwald RA, Street RT, Pruzanski W. (1991). Inhibition of synovial fluid phospholipase A2 activity by two tetracycline derivatives, minocycline and doxycycline. Arthrit Rheum34:160-164.
19.
Vane JR, Mitchell JA, Appleton I., Tomlinson A., Bishop-Bailey D., Croxtall J., et al. (1994). Inducible isoforms of cyclooxygenase and nitric oxide synthase in inflammation. Proc Natl Acad Sci USA91:2046-2050.
20.
Webster GF, Toso SM, Hegemann L. (1994). Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin. Involvement of protein kinase C. Arch Dermatol130:748-752.