Objective      To evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of monocyte chemoattractant protein-1 (MCP-1) in 3T3-L1 adipocytes induced by oxidized low-density lipoprotein (oxLDL).       Methods      Fully differentiated 3T3-L1 adipocytes were preincubated in the medium containing different concentrations of L-4F (0

1

10

and 50 μg/ml)

H-89 (10 μmol/L) and H-89 (10 μmol/L) combined with L-4F (50 μg/ml)

respectively. Then the adipocytes were treated by oxLDL (50 μg/ml). The concentration of MCP-1

the mRNA expression of MCP-1

and the protein levels of CCAAT/enhancer binding protein (C/EBP)α and C/EBPβ in cell supernatant were evaluated. The effect of the supernatant on the chemotactic activity of human peripheral blood monocytes was detected by micropore filter method using a modified Boyden chamber.       Results      OxLDL (50 μg/ml) treatment induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes

and the mean of migration distance of human peripheral blood monocytes induced by the cell supernatant was significantly longer than that of the random migration group. MCP-1 secretion and expression as well as the chemotactic activity of human peripheral blood monocyte were decreased by the L-4F pre-incubation in a dose-dependent manner. MCP-1 expression in the adipocytes pretreated with L-4F (50 μg/ml) decreased by (91±6)% (P0.01). PKA inhibitor H-89 (10 μmol/L) significantly reduced the oxLDL-induced MCP-1 expression (P0.01)

but no further decrease was observed when H-89 (10 μmol/L) was used in combination with L-4F (50 μg/ml) (P0.05). OxLDL (50 μg/ml) treatment showed no significant effect on C/EBPα content

but increased C/EBPβ content in a time-dependent manner. H-89 and L-4F both attenuated C/EBPβ protein content in oxLDL-treated 3T3-L1 adipocytes.       Conclusion      OxLDL induces C/EBPβ protein synthesis and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes in a time-dependent manner. L-4F dose-dependently counterbalances the proinflammatory effect of oxLDL

which may involve cAMP/PKA-C/EBPβ signaling pathway.