Inhibition of interleukin-8 production in the human colonic epithelial cell line HT-29 by 18 beta-glycyrrhetinic acid.
Interleukin (IL)-8 plays a central role in the initiation and maintenance of inflammatory responses in the inflammatory bowel disease. The proinflammatory cytokine-mediated production of IL-8 requires activation of various kinases, which leads to the I kappa B degradation and NF-kappa B activation. We investigated the role of 18 beta-glycyrrhetinic acid (GA), a saponin isolated from licorice roots, on TNF-alpha-induced IL-8 production in human colonic epithelial cells. HT29 cells were stimulated with TNF-alpha in the presence or absence of GA (1, 5 or 10 microM). IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction analysis, and the mitogen-activated protein kinases (MAPKs) activation and I kappa B alpha degradation were determined by Western blot analysis. GA suppressed TNF-alpha-induced IL-8 production in a concentration-dependent manner. In addition, GA inhibited TNF-alpha-induced phosphorylation of p38 MAPK and extracellular-regulated kinases (ERK), I kappa B alpha degradation, and NF-kappa B activation. These results suggest that GA has the inhibitory effects on TNF-alpha-induced IL-8 production in the intestinal epithelial cells through blockade in the phosphorylation of MAPKs, following I kappa B alpha degradation and NF-kappa B activation.
Kang
Ok-Hwa
OH
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, Korea.
Kim
Jin-A
JA
Choi
Yeon-A
YA
Park
Hye-Jung
HJ
Kim
Dae-Ki
DK
An
Yong-Hwan
YH
Choi
Suck-Chei
SC
Yun
Ki-Jung
KJ
Nah
Yong-Ho
YH
Cai
Xing Fu
XF
Kim
Young-Ho
YH
Bae
Ki-Hwan
KH
Lee
Young-Mi
YM
D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D006034:Glycyrrhetinic Acid