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Tumor-secreted factors induce IL-1? maturation via the glucose-mediated synergistic axis of mTOR and NF-?B pathways in mouse macrophages.

ABSTRACT: Macrophages are one of the major cell types that produce IL-1?. IL-1? maturation occurs via inflammasome activation, and mature IL-1? is then released from the cell. Secreted IL-1? mediates inflammatory reactions in various pathological environments, such as those in infectious, autoimmune, and cancerous diseases. Although the mechanism of IL-1? production has been discovered in infectious and autoimmune diseases, its production mechanism in the tumor microenvironment is unclear. Therefore, the mechanism of IL-1? production in macrophages in the tumor microenvironment was investigated in this study. First, bone marrow-derived macrophages obtained from C57BL/6 mice were treated with B16F10 tumor-conditioned media (TCM) in vitro. TCM increased the levels of IL-1? via glucose-mediated activation of the inflammasome. Moreover, TCM enhanced the activation of both NF-?B and mTOR pathways in a glucose-dependent manner. In particular, the expression levels of mTORC1 component proteins were dependent on the TCM-induced activation of NF-?B signaling. In addition, TCM affected ASC-ASC interactions through increasing intracellular reactive oxygen species levels. Finally, glucose inhibition by inoculation with 2-deoxy-D-glucose in vivo decreased the IL-1? levels in both the blood and tumor region of B16F10-bearing C57BL/6 mice relative to those in PBS-injected tumor-bearing mice. These results suggest that glucose supplied from blood vessels might be important for IL-1? production in tumor-associated macrophages via the integrated signals of the NF-?B and mTOR pathways in the tumor microenvironment.

SUBMITTER: Woo Y

PROVIDER: S-EPMC6306269 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Tumor-secreted factors induce IL-1β maturation via the glucose-mediated synergistic axis of mTOR and NF-κB pathways in mouse macrophages.

Woo Yunseo Y Kim Hyeran H Kim Keun-Cheol KC Han Jeong A JA Jung Yu-Jin YJ

PloS one 20181226 12

Macrophages are one of the major cell types that produce IL-1β. IL-1β maturation occurs via inflammasome activation, and mature IL-1β is then released from the cell. Secreted IL-1β mediates inflammatory reactions in various pathological environments, such as those in infectious, autoimmune, and cancerous diseases. Although the mechanism of IL-1β production has been discovered in infectious and autoimmune diseases, its production mechanism in the tumor microenvironment is unclear. Therefore, the ...[more]

PMID: 30586442

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Dataset Information

Tumor-secreted factors induce IL-1? maturation via the glucose-mediated synergistic axis of mTOR and NF-?B pathways in mouse macrophages.

Publications

Tumor-secreted factors induce IL-1β maturation via the glucose-mediated synergistic axis of mTOR and NF-κB pathways in mouse macrophages.

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