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- Title
Inhibitory effect of carbazolequinone derivatives on lipopolysaccharide and interferon-γ-induced nitric oxide production in mouse macrophage RAW264.7 cells.
- Authors
Murata, Tomiyasu; Kohno, Susumu; Ito, Chihiro; Itoigawa, Masataka; Sugiura, Ayumi; Hikita, Kiyomi; Kaneda, Norio
- Abstract
Objectives The aim of this study was to examine the mechanism underlying the inhibitory effect of our synthesized carbazolequinone derivatives on nitric oxide ( NO) production in activated macrophages. Methods Lipopolysaccharide ( LPS) and interferon-γ ( IFN-γ)-stimulated RAW264.7 macrophages were treated with carbazolequinone derivatives. The NO and prostaglandin E2 ( PGE2) levels in cell culture supernatants fractions were measured by Greiss and ELISA assay, respectively. The expression of inducible NO synthase (i NOS) and cyclooxygenase-2 ( COX-2) was assessed by the real-time RT-PCR method. Nuclear factor kappa B ( NF-κ B) activation was detected by an NF-κ B-dependent luciferase reporter assay. Key findings Our synthesized carbazolequinone derivatives (7-methoxy-2-methylcarbazole-1,4-quinone, 6-methoxy-2-methylcarbazole-1,4-quinone and 6-chloro-2-methylcarbazole-1,4-quinone) significantly inhibited LPS/ IFN-γ-induced NO production and i NOS expression in RAW264.7 cells. They also inhibited the LPS/ IFN-γ-mediated induction of COX-2 expression and PGE2 production. In addition, the LPS/ IFN-γ-induced transcription activity of NF-κ B was attenuated. Using the RAW264.7-ts AM5NE co-culture system, we found that these carbazolequinone derivatives protected neuronally differentiated ts AM5NE cells from NO-induced cell death by inhibiting the production of NO. Conclusions These results suggest that the three carbazolequinone derivatives inhibit LPS/ IFN-γ-induced NO production via i NOS and COX-2 downregulation due to NF-κ B inhibition. Therefore, these three carbazolequinone derivatives may be useful for developing a new drug against NO-mediated neurodegenerative diseases.
- Subjects
NITRIC oxide; LIPOPOLYSACCHARIDES; DINOPROSTONE; CYCLOOXYGENASE 2; MACROPHAGES; LUCIFERASES
- Publication
Journal of Pharmacy & Pharmacology, 2013, Vol 65, Issue 8, p1204
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/jphp.12087