Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways

Hong-Tao Liu, Jun-Lin He, Wen-Ming Li, Zhu Yang, Ying-Xiong Wang, Juan Yin, Yu-Guang Du, Chao Yu
Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.] 2010, 59 (6): 451-61

OBJECTIVE: The aim of this study was to investigate the inhibitory effect of geniposide on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and interleukin-8 (IL-8) production in human umbilical vein endothelial cells (HUVECs).

MATERIALS AND METHODS: Primary HUVECs were used. The mRNA/protein levels of IL-6 and IL-8 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). LPS-induced HUVEC migration and adhesion of monocytes to HUVECs were studied by monolayer wound healing experiments and monocytic cell adhesion assay, respectively. Expression of nuclear factor kappaB (NF-kappaB), inhibitory factor kappaB-alpha (IkappaB-alpha), p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were determined by Western blot analysis.

RESULTS: Geniposide effectively inhibited LPS-induced expression of IL-6 and IL-8 in HUVECs at the transcription and translation levels. Additionally, geniposide suppressed LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs. Signal transduction studies indicate that geniposide blocked the activation of NF-kappaB, degradation of IkappaB-alpha, and phosphorylation of p38 MAPK and ERK1/2 in HUVECs challenged by LPS.

CONCLUSION: The results show that geniposide can inhibit LPS-induced IL-6 and IL-8 production in HUVECs by blocking p38 MAPK and ERK1/2 signaling pathways.

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