Interleukin-10 up-regulates tumour-necrosis-factor-α-related apoptosis-inducing ligand (TRAIL) gene expression in mammary epithelial cells at the involution 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 highest 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 seven transgenic lines at the lactation stage. It was striking that the expression of tumour-necrosis-factor-α-related apoptosis-inducing ligand (TRAIL) among the apoptosis-related genes was elevated approx. 7-fold in the transgenic mice, whereas others were almost unchanged. Furthermore, TRAIL was down-regulated 4-fold in the IL-10^-/- mice at the involution stage. Elevated expression of TRAIL and of death receptor 4 (DR4) protein was identified at the involution stage of normal mammary glands as well as at the lactation stage of the IL-10 transgenic mice. These results indicate that the elevated expression of IL-10 at the involution stage recruits lymphocytes and induces the expression of TRAIL and DR4. These phenomena might partly contribute to apoptosis in the mammary epithelial cells for entering involution.