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

ABSTRACT: 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.

SUBMITTER: Sohn BH

PROVIDER: S-EPMC1222199 | biostudies-other | 2001 Nov

REPOSITORIES: biostudies-other

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Two-stage nanoparticle delivery of piperlongumine and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) anti-cancer therapy.

Project description:This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.

| S-EPMC5108302 | biostudies-literature

Inhibition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension.

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| S-EPMC3478928 | biostudies-literature

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| S-EPMC6791380 | biostudies-literature

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| S-EPMC7476262 | biostudies-literature

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| S-EPMC10810846 | biostudies-literature

Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis.

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| S-EPMC3426075 | biostudies-literature

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| S-EPMC3195575 | biostudies-literature

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| S-EPMC3375548 | biostudies-literature

Single-cell RNAseq profiling of HeLa cells after stimulation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Project description:HeLa cells were treated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL: 10, 25 or 40ng/ml) or with the drug vehicle ("Control"), for 50 minutes or 2 hours prior to analyses by single-cell RNA sequencing. The objective was to study the extent of gene expression variability in resting cells and to evaluate the effect of time and dose of TRAIL treatments on gene expression variability.

2020-09-23 | GSE138833 | GEO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro.

Project description:The molecular events regulating the elimination of cells to create a hollow lumen during tissue development are poorly understood. By using an in vitro morphogenesis model in which MCF-10A human mammary epithelial cells form hollow acini-like structures, we have observed both caspase-mediated apoptosis and autophagy associated with cells that are lost during lumen formation. Here, we show that the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates induction of autophagic processes associated with lumen formation. TRAIL is up-regulated during morphogenesis of MCF-10A mammary epithelial cells in 3D basement-membrane cultures and inhibition of TRAIL signaling during morphogenesis blocks the formation of autophagic vacuoles. In addition, treatment with exogenous TRAIL induces extensive autophagy in monolayer and 3D cultures. When combined with inhibition of caspase 3 activity (by Bcl-X(L) overexpression), inhibition of TRAIL-induced autophagy results in luminal filling. Thus, TRAIL regulates an autophagic program during acinar morphogenesis, which together with caspase-mediated apoptotic events, results in lumen formation during MCF-10A morphogenesis.

| S-EPMC373480 | biostudies-literature

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