Inhibition of TNF-alpha and IL-6 production by Aucubin through blockade of NF-kappaB activation RBL-2H3 mast cells.
Antigen (Ag)-stimulated mast cells induce synthesis and production of cytokines including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 with proinflammatory and immune regulatory properties. Expression of TNF-alpha and IL-6 was regulated by a transcription factor, nuclear factor (NF)-kappaB. The iridoid glycoside, aucubin, has been found as a natural constituent of many traditional oriental medicinal plants. We studied the effect of aucubin on the TNF-alpha and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-alpha and IL-6 production and expression in a dose-dependent manner with IC(50) of 0.101 and 0.19 microg/ml, respectively. Maximal inhibition of TNF-alpha and IL-6 production was 73 +/- 4.3% and 88.8 +/- 5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-kappaB and degradation of IkappaBalpha. Inhibition of NF-kappaB activation by aucubin might be specific since activator protein-1 binding activity was not affected. In conclusion, these results suggest that aucubin is a specific inhibitor of NF-kappaB activation in mast cells, which might explain its beneficial effect in the treatment of chronic allergic inflammatory diseases.
Jeong
Hyun-Ja
HJ
Department of Oriental Pharmacy, College of Pharmacy and Korea Institute of Oriental Pharmacy, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea.
Koo
Hyun-Na
HN
Na
Ho-Jeong
HJ
Kim
Mi-Sun
MS
Hong
Seung-Heon
SH
Eom
Jung-Woo
JW
Kim
Kyung-Suk
KS
Shin
Tae-Yong
TY
Kim
Hyung-Min
HM
D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D015850:Interleukin-6 / Q000096:biosynthesis*; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D005960:Glucosides; D006632:Histamine; D020672:I-kappa B Proteins; D015850:Interleukin-6; D057888:Iridoid Glucosides; D039823:Iridoids; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D001619:beta-N-Acetylhexosaminidases; D000093242:Interleukin-6 Inhibitors; C000606206:Nfkbia protein, rat; C006650:aucubin