Objective       To determine the effects of micromolar copper (ii) ions (Cu

2+

) on the proliferation and the generation of reac

tive oxygen species (ROS) in human skin keratinocyte line HaCaT

and verify their relationship through ROS scavenger

N-Acetyl-L-cysteine (NAC).        Methods       HaCaT cells were treated with different concentrations of copper (ii) ions (0

10

-8

10

-7

10

-6

10

-5

10

-4

and 10

-3

mol/L) in presence or absence of 5 mmol/L NAC. Cell counting kit-8 (CCK-8) assay and fluorescent probe DCFH-DA were used to measure the cell proliferation and ROS generation in the HaCaT cells

respectively. Laser confocal microscopy was employed to observe the intracellular ROS levels and mitochondria localization in the cells.       Results       After cultured with 10

-6

and 10

-5

mol/L Cu

2+

for 48 h

the cell relative proliferation rates reached 116.19% (P=0.027) and 113.37% (P=0.036) respectively

and were significantly higher than that in negative control cells (0 mol/L Cu

2+

). Meanwhile

after exposure to 10

-6

and 10

-5

mol/L Cu

2+

the generation of intracellular ROS was remarkably increased to 127.47% (P=0.001) and 124.27% (P=0.031) at 30 min

and 140.47% (P=0.002) and 134.29% (P=0.007) at 60 min respectively. In addition

5 mmol/L NAC significantly antagonized the cell proliferation and ROS generation induced by Cu

2+

. Although intracellular ROS generation was also increased to 110.99% (P=0.016) and 117.34% (P=0.016) after 60 min exposure under 10

-8

and 10

-7

mol/L Cu

2+

the cell relative proliferation rates were only 101.09% and 101.86%

and no obvious change was observed in keratinocyte proliferation in these 2 groups and blank cells (both P0.05).       Conclusion       Micromolar copper (ii) ions promote the proliferation of human skin keratinocyte through up-regulating ROS generation at moderate level.