Dataset Information

The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling.

ABSTRACT:

Introduction

Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied.

Methods

qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle^-/- mice.

Results

TDB treatment up-regulated M1 markers over M2 markers by GM-CSF BMMs, whereas M-CSF/IL-4 BMMs down-regulated marker gene expression overall. TDB treatment resulted in Mincle-independent down-regulation of CD11b, CD115, and CD206 expression by GM-CSF macrophages and CD115 in M-CSF/IL-4 macrophages. GM-CSF BMMs produced of significant levels of proinflammatory cytokines (IL-1?, IL-6, TNF-?), which was Mincle-dependent and further enhanced by LPS priming. M-CSF BMMs produced little or no cytokines in response to TDB regardless of LPS priming. Western blot analysis confirmed that the absence of cytokine production was associated with a lack of activation of the Syk kinase pathway.

Conclusion

This study illustrates that TDB has the potential to differentially regulate M1- and M2-like macrophages in the tumor environment.

SUBMITTER: Kodar K

PROVIDER: S-EPMC5691301 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling.

Kodar Kristel K Harper Jacquie L JL McConnell Melanie J MJ Timmer Mattie S M MSM Stocker Bridget L BL

Immunity, inflammation and disease 20170719 4

<h4>Introduction</h4>Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied.<h4>Methods</h4>qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 deriv ...[more]

PMID: 28722316

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Dataset Information

The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling.

Introduction

Methods

Results

Conclusion

Publications

The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling.

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