Interleukin-10 up-regulates tumour-necrosis-factor-alpha-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-alpha-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.
Sohn
B H
BH
Animal Developmental Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-333, Korea.
Moon
H B
HB
Kim
T Y
TY
Kang
H S
HS
Bae
Y S
YS
Lee
K K
KK
Kim
S J
SJ
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism*; D016923:Cell Death; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D007774:Lactation; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D012260:Ribonucleases