Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cell by blocking ERK, p38 and nulear factor-kappaB signaling pathways.
OBJECTIVE
To determine the anti-inflammatory effects of Tetramethylpyrazine (TMP) and to investigate the inhibitory effect of TMP on IL-8 production in human umbilical vein endothelial cells (HUVECs) induced by LPS might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways.


METHODS
HUVECs were treated with or without TMP for 24h before exposure to LPS for 4h. IL-8 gene and protein expressions were determined by RT-PCR and ELISA. Cell viability was determined by methyl thiazoyltetrazolium (MTT) assay. Phosphorylation of ERK1/2 and p38 were examined by western blotting.


RESULTS
TMP inhibits LPS-induced IL-8 production in HUVECs at both the protein and mRNA levels, suggesting that TMP has an antiinflammatory effect on endothelial cells. TMP also inhibited U937 monocyte adhesion to HUVECs stimulated by LPS. LPS-induced phosphorylation of ERK1/2 and p38 were inhibited by TMP. The inhibitory effect of TMP on NF-kappaB (p65) activity was mediated by blocking the consequent translocation of p65 into the nucleus.


CONCLUSIONS
The inhibitory effect of TMP on the LPS-induced IL-8 production is mediated by the NF-kappaB-dependent pathway, and TMP also separately affects the ERK and p38 MAPK pathway. TMP may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis.
Li
Xiu-Ying
XY
Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
He
Jun-Lin
JL
Liu
Hong-Tao
HT
Li
Wen-Ming
WM
Yu
Chao
C
D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D011719:Pyrazines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells; D014471:Umbilical Veins / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D003470:Culture Media; D017931:DNA Primers; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011719:Pyrazines; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C017953:tetramethylpyrazine