KIOM-79 inhibits LPS-induced iNOS gene expression by blocking NF-kappaB/Rel and p38 kinase activation in murine macrophages.
We demonstrate that KIOM-79, combined extracts obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of RAW 264.7 cells with KIOM-79 inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohisto-chemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Immunostaining of p65, EMSA, and reporter gene assay showed that KIOM-79 inhibited NF-kappa/Rel nuclear translocation, DNA binding, and transcriptional activation, respectively. Western immunoblot analysis of p38 kinase showed KIOM-79 significantly inhibited the phosphoylation of p38 kinase which is important in the regulation of iNOS gene expression. Collectively, this series of experiments indicates that KIOM inhibits iNOS gene expression by blocking NF-kappa/Rel and p38 kinase signaling. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of KIOM-79 on iNOS suggest that KIOM-79 may represent a useful anti-inflammatory agent.
Jeon
Young Jin
YJ
College of Medicine, Chosun University, 375 Susukdong, Kwangju 501-709, Republic of Korea.
Li
Mei Hong
MH
Lee
Kun Yeong
KY
Kim
Jin Sook
JS
You
Ho Jin
HJ
Lee
Seog Ki
SK
Sohn
Hong Moon
HM
Choi
Sang Joon
SJ
Koh
Jae Woong
JW
Chang
In Youb
IY
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D029882:Glycyrrhiza uralensis / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D031566:Magnolia / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020569:Proto-Oncogene Proteins c-rel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C517978:KIOM 79; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D020569:Proto-Oncogene Proteins c-rel; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases