Abstract: Objective To investigate the effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in human
macrophages and the membrane potential and foaming process of the macrophages. Methods The effect of diclofenac on the
expression of Kv1.3 and Kir2.1 channels in cultured human monocyte-derived macrophages was investigated using real-time
RT-PCR and Western blotting, and its effect on the membrane potential was analyzed with optical mapping of the membrane
potential with voltage-sensitive dyes. The ratio of cholesterol ester (CE) in the macrophages following intake of oxidized
low-density lipoprotein (OxLDL) was analyzed by an enzymatic fluorometric method. Results The expression of Kv1.3 and
Kir2.1 channels in the macrophages were down-regulated by diclofenac (1.5 μmol/L and 15 μmol/L). Compared with those in
the control group, Kv1.3 mRNA expression was reduced by over 80% and 90% (P<0.05), and Kir2.1 mRNA by over 20% and
30% (P>0.05), respectively; both their protein expression was reduced by over 10% and 60% with a dose- dependent effect (P<
0.05). Diclofenac at the two doses dose-dependently reduced the surface fluorescence intensity of the macrophage, and the
membrane potential was decreased by 28% and 54%, respectively (P<0.05). Incubation of the macrophages with 30 mg/L
OxLDL for 60 h caused an obvious enlargement of the cell volume and deposition of numerous lipid granules in cytoplasm,
resulting also in a CE/TC ratio over 50% (P<0.05). Diclofenac at 1.5 and 15 μmol/L both significantly decreased the CE/TC ratio
to (23.624±3.34)% and (13.601±2.916)% (P<0.05), respectively, but this effect did not show a dose-response relationship (P>0.05).
Conclusion Diclofenac can significant down-regulate the expression of Kv1.3 and Kir2.1 channels in human macrophages,
lower their membrane potential and inhibit the process of foam cell formation.