Premium
Paeoniflorin suppresses the expression of intercellular adhesion molecule‐1 (ICAM‐1) in endotoxin‐treated human monocytic cells
Author(s) -
Jin Lei,
Zhang LiMin,
Xie KeQiang,
Ye Yang,
Feng Linyin
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01464.x
Subject(s) - u937 cell , icam 1 , umbilical vein , intercellular adhesion molecule 1 , chemistry , paeoniflorin , receptor , microbiology and biotechnology , adenosine a2a receptor , monocytic leukemia , tumor necrosis factor alpha , biology , intracellular , adenosine receptor , biochemistry , endocrinology , cell culture , in vitro , high performance liquid chromatography , chromatography , genetics , agonist
BACKGROUND AND PURPOSE Paeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti‐inflammatory property. Abnormally high levels of intercellular adhesion molecule‐1 (ICAM‐1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM‐1 elevated in LPS‐activated differentiated human monocytic U937 cells and TNF‐α‐stimulated human umbilical vein endothelial cells (HUVECs). EXPERIMENTAL APPROACH mRNA levels were evaluated by RT‐PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF‐κB translocation, and NF‐κB binding to nuclear DNA was determined by EMSA. KEY RESULTS PF inhibited ICAM‐1 expression elevated in LPS‐induced U937 cells and TNF‐α‐stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A 1 receptors, application of a selective adenosine A 1 receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM‐1 expression. PF suppressed the activation of the NF‐κB pathway, which regulates the expression of ICAM‐1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells. CONCLUSIONS AND IMPLICATIONS PF inhibits ICAM‐1 expression in LPS‐treated U937 cells and TNF‐α‐stimulated HUVECs by suppressing the activation of the NF‐κB pathway.