Interleukin-10 up-regulates tumour-necrosis-factor-alpha-related apoptosis-inducing ligand (TRAIL) gene expression in mammary epithelial cells at theinvolution stage

Although interleukin-10 (IL-10) is known to contribute to inflammation and pathogenesis in mammalian organs, little is known about its precise role in the mammary gland. We found that IL-10 levels fluctuated during the mouse mammary cycle, showing little expression at the lactation stage and the hig hest expression at the involution stage. To reveal the effects of IL-10 on involution, expression profiles of apoptosis-related genes were examined in mice transgenic for IL-10 as well as in IL-10(-/-) mice. Mild inflammatory lesions by lymphocytes were observed in the mammary glands from four of se ven transgenic lines at the lactation stage. It was striking that the expre ssion of tumour-necrosis-factor-alpha -related apoptosis-inducing ligand (T RAIL) among the apoptosis-related genes was elevated approx. 7-fold in the transgenic mice, whereas others were almost unchanged. Furthermore, TRAIL w as down-regulated 4-fold in the IL-10(-/-) mice at the involution stage. El evated expression of TRAIL and of death receptor 4 (DR4) protein was identi fied at the involution stage of normal mammary glands as well as at the lac tation stage of the IL-10 transgenic mice. These results indicate that the elevated expression of IL-10 at the involution stage recruits lymphocytes a nd induces the expression of TRAIL and DR4. These phenomena might partly co ntribute to apoptosis in the mammary epithelial cells for entering involuti on.