DA-9601 inhibits activation of the human mast cell line HMC-1 through inhibition of NF-kappaB.
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.
Lee
S
S
Department of Pharmacology, Kyungpook National University Medical School, Daegu, Korea.
Park
H-H
HH
Son
H-Y
HY
Ha
J-H
JH
Lee
M-G
MG
Oh
T-Y
TY
Sohn
D H
DH
Jeong
T C
TC
Lee
S H
SH
Son
J-K
JK
Lee
S G
SG
Jun
C-D
CD
Kim
S-H
SH
D019306:Artemisia; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; C116959:DA 9601; D018836:Inflammation Mediators; D016328:NF-kappa B; D010936:Plant Extracts; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate