Penta-O-galloyl-beta-D-glucose inhibits phorbol myristate acetate-induced interleukin-8 [correction of intereukin-8] gene expression in human monocytic U937 cells through its inactivation of nuclear factor-kappaB.
We investigated the effects of the gallotannin penta-O-galloyl-beta-d-glucose (PGG) on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. PGG inhibited IL-8 production and gene expression in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA), as measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction analysis, respectively. PGG also inhibited PMA-mediated NF-kappaB activation, as measured by electromobility shift assay. Furthermore, PGG prevented PMA-mediated degradation of the NF-kappaB inhibitory protein I-kappaBalpha, as measured by Western blot analysis. PGG also inhibited both IL-8 production and NF-kappaB activation in the U937 cells stimulated with tumor necrosis factor-alpha. These results suggest that PGG, a major constituent of the root cortex of Paeonia suffruticosa ANDREWS, can inhibit IL-8 gene expression by a mechanism involving its inhibition of NF-kappaB activation, which is dependent on I-kappaBalpha degradation.
Oh
G S
GS
Department of Microbiology and Immunology, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan-Shi, Chonbuk 570-749, South Korea.
Pae
H O
HO
Choi
B M
BM
Lee
H S
HS
Kim
I K
IK
Yun
Y G
YG
Kim
J D
JD
Chung
H T
HT
D021581:Active Transport, Cell Nucleus; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D020298:U937 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047348:Hydrolyzable Tannins; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C435084:pentagalloylglucose; D013755:Tetradecanoylphorbol Acetate