Inhibition of nitric oxide and tumor necrosis factor-alpha (TNF-alpha) production by propenone compound through blockade of nuclear factor (NF)-kappa B activation in cultured murine macrophages.
Lipopolysaccharide (LPS)-stimulated macrophages produce large amounts of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). This is an important mechanism in macrophage-induced septic shock and inflammation. In the present study, we tested a synthetic propenone compound, 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) for its ability to inhibit the production of tumor necrosis factor-alpha (TNF-alpha) and an inducible enzyme, iNOS, in the LPS-stimulated murine macrophage-like cell line, RAW264.7. FPP-3 consistently inhibited nitric oxide (NO) and TNF-alpha production in a dose dependent manner, with IC(50) values of 10.0 and 13.1 microM, respectively. Western blotting probed with specific anti-iNOS antibodies showed that the decrease in quantity of the NO product was accompanied by a decrease in the iNOS protein level. In cells transiently transfected with nuclear factor (NF)-kappaB promoter-luciferase reporter construct, this compound clearly inhibited the LPS-stimulated NF-kappaB activation. Moreover, this compound inhibited IkappaB-alpha degradation in a concentration and time-dependent manner. These results indicate that FPP-3 inhibits NO production via inhibition of degradation of IkappaB-alpha through NF-kappaB activation.
Lee
Eung-Seok
ES
College of Pharmacy, Yeungnam University, Gyongsan, South Korea.
Ju
Hye Kyung
HK
Moon
Tae Churl
TC
Lee
Eunkyung
E
Jahng
Yurngdong
Y
Lee
Sung Ho
SH
Son
Jong Keun
JK
Baek
Suk-Hwan
SH
Chang
Hyeun Wook
HW
D000818:Animals; D002460:Cell Line; D005663:Furans / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D005663:Furans; D016328:NF-kappa B; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide