Inhibition of TNF-alpha and IL-6 production by Aucubin through blockade of NF-kappaB activation RBL-2H3 mast cells.

Abstract

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.

• Authors: Hyun-Ja Jeong, Hyun-Na Koo, Ho-Jeong Na, Mi-Sun Kim, Seung-Heon Hong, Jung-Woo Eom, Kyung-Suk Kim, Tae-Yong Shin, Hyung-Min Kim
• Journal: Cytokine (Cytokine) Vol. 18 Issue 5 Pg. 252-9 (Jun 07 2002) ISSN: 1043-4666 [Print] England
• PMID: 12161100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucosides
• I-kappa B Proteins
• Interleukin-6
• Iridoid Glucosides
• Iridoids
• NF-kappa B
• Nfkbia protein, rat
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• NF-KappaB Inhibitor alpha
• aucubin
• Histamine
• beta-N-Acetylhexosaminidases

Topics

• Animals
• Blotting, Western
• Cell Nucleus (metabolism)
• Dose-Response Relationship, Drug
• Glucosides (pharmacology)
• Histamine (metabolism)
• I-kappa B Proteins (metabolism)
• Immunohistochemistry
• Inhibitory Concentration 50
• Interleukin-6 (antagonists & inhibitors, biosynthesis)
• Iridoid Glucosides
• Iridoids (pharmacology)
• Microscopy, Fluorescence
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Transcription Factor RelA
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis)
• beta-N-Acetylhexosaminidases (metabolism)