Concomitant induction of apoptosis and expression of monocyte chemoattractant protein‐1 in cultured rat luteal cells by nuclear factor‐κB and oxidative stress

It has previously been shown that expression of monocyte chemoattractant protein (mcp)-1 and apoptosis of luteal cells occur concomitantly during the estrous cycle in the rat corpus luteum; however, luteal cells containing mcp-1 mRNA did not seem to be apoptotic. In the present study, the relationship between the induction of apoptosis and mcp-1 expression in cultures of dispersed rat luteal cells was examined. Both apoptosis and mcp-1 expression were spontaneously induced in cultured luteal cells in a manner inhibitable by antioxidative reagents or an inhibitor of nuclear translocation of nuclear factor-kB. However, the cells containing mcp-1 mRNA were distinct from those undergoing apoptosis, and the inhibition of apoptosis by the pan-caspase inhibitor z-VAD-fmk did not influence the induction of mcp-1 expression. These results collectively indicate that oxidative stress simultaneously, but independently, induces apoptosis and mcp-1 expression in luteal cells through the activation of nuclear factor-kB. This phenomenon might help to explain how monocytes/macrophages accumulate in regressive corpora lutea where their target apoptotic cells exist.