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2246517 
Journal Article 
Inhibition of lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages by a synthetic carbazole, LCY-2-CHO 
Tsao, LT; Lee, CY; Huang, LJ; Kuo, SC; Wang, HP 
2002 
Yes 
Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 
63 
11 
1961-1968 
English 
12093472 
WOS:000177112500005 
In activated macrophages, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS). This is an important mechanism in macrophage-induced cytotoxicity and inflammation. In the present study, a synthetic carbazole compound, 9-(2-chlorobenzyl)-9H-carbazole-3-carbaldehyde (LCY-2-CHO), was found to have an inhibitory effect on lipopolysaccharide (LPS)-stimulated NO generation in RAW 264.7 macrophages (IC50 value of 1.3+/-0.4 microM). LCY-2-CHO did not induce cytotoxicity and had a negligible effect on iNOS activity. To explore the mechanism of inhibition of NO generation by LCY-2-CHO, the expression of the iNOS gene was examined. LCY-2-CHO abolished the LPS-induced expression of both iNOS protein and mRNA in a parallel concentration-dependent manner with IC50 values similar to those required for inhibition of NO generation. LCY-2-CHO did not enhance the degradation of iNOS mRNA. In cells transiently transfected with an iNOS promoter-chloramphenicol acetyltransferase (CAT) reporter construct, LCY-2-CHO attenuated the LPS-induced iNOS promoter activity. However, LCY-2-CHO had no effect on the degradation of IkappaB-alpha or IkappaB-beta, DNA binding activity, or transcriptional activity of nuclear factor-kappaB (NF-kappaB). These results indicate that LCY-2-CHO inhibits NO generation via a decrease in the transcription of iNOS mRNA through a signaling pathway that does not involve NF-kappaB activation. 
RAW 264.7; LCY-2-CHO; nitric oxide; inducible nitric oxide synthase; NF-kappa B