Bee venom suppresses LPS-mediated NO/iNOS induction through inhibition of PKC-alpha expression.
BACKGROUND
Bee venom (BV) is a traditional Korean medicine that has been widely used with satisfactory results in the treatment of some immune-related diseases, especially rheumatoid arthritis.


OBJECTIVE
The purpose of this study is to elucidate the molecular mechanism underlying the anti-inflammatory effects of BV, which is used in the treatment of various inflammatory diseases in traditional Korean medicine. We evaluated the anti-inflammatory effect of BV on NO generation and iNOS expression by LPS in rat C6 glioma cells.


METHODS
BV was obtained from the National Institute of Agricultural Science and Technology (NIAST) of Korea. Nitrite measurement, Immuno blot analysis, Reverse transcriptase-PCR and Electrophoretic mobility shift assay (EMSA) were used for assessment.


RESULTS
BV suppressed the LPS-induced NO generation and iNOS expression, and it also inhibited the expressions of LPS-induced pro-inflammatory molecules including Cox-2 and IL-1 beta in rat C6 glioma cells. Then, BV inhibited LPS-induced expression of PKC-alpha and MEK/ERK, not p38 and JNK. Moreover, inhibition of LPS-induced iNOS expression by BV was dependent on transcriptional activities of AP-1/NF-kappaB through MEK/ERK pathway.


CONCLUSIONS
These results indicate that BV suppresses LPS-induced iNOS activation through regulation of PKC-alpha. Accordingly, BV exerts a potent suppressive effect on pro-inflammatory responses in rat C6 glioma cells.
Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon, Kyunggi-Do 441-100, Republic of Korea.
Kwang-Gill
KG
Lee
Hyun-Ji
HJ
Cho
Young-Seuk
YS
Bae
Kwan-Kyu
KK
Park
Jung-Yoon
JY
Choe
Il-Kyung
IK
Chung
Mihyun
M
Kim
Joo-Hong
JH
Yeo
Kyung-Ho
KH
Park
Yun-Sik
YS
Lee
Cheorl-Ho
CH
Kim
Young-Chae
YC
Chang
D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D004790:Enzyme Induction; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001514:Bee Venoms; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051571:Protein Kinase C-alpha