Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase.
Algal fucoidan is a marine sulfated polysaccharide with a wide variety of biological activities including anti-thrombotic and anti-inflammatory effects. This study evaluated the effect of fucoidan on the expression of inducible nitric oxide synthase (iNOS) in a macrophage cell line, RAW264.7. Low concentration range of fucoidan (10 microg/ml) increased the basal expression level of iNOS in quiescent macrophages. However, we found for the first time that fucoidan inhibited the release of nitric oxide (NO) in RAW264.7 cells stimulated with lipopolysaccharide (LPS). Western blot analysis revealed that fucoidan suppressed the LPS-induced expression of the inducible nitric oxide synthase (iNOS) gene. Moreover, the activation of both nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) are key steps in the transcriptional activation of the iNOS gene. Here, it was revealed that fucoidan selectively suppressed AP-1 activation, and that the activation of AP-1 appears to be essential for the induction of iNOS in activated macrophages. This inhibitory effect on AP-1 activation by fucoidan might be associated with its NO blocking and anti-inflammatory effects.
Yang
Jin Won
JW
College of Pharmacy, Chosun University, Gwangju, South Korea.
Yoon
Se Young
SY
Oh
Soo Jin
SJ
Kim
Sang Kyum
SK
Kang
Keon Wook
KW
D000818:Animals; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D011134:Polysaccharides / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation
D008070:Lipopolysaccharides; D016328:NF-kappa B; D011134:Polysaccharides; D018808:Transcription Factor AP-1; C007789:fucoidan; D052247:Nitric Oxide Synthase Type II