Ethanol Extract of Mylabris phalerata Inhibits M2 Polarization Induced by Recombinant IL-4 and IL-13 in Murine Macrophages.

Hwan-Suck Chung,Jin Yeul Ma,Bong-Seon Lee

doi:10.1155/2017/4218468

Abstract

Mylabris phalerata (MP) is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM) have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment. In this line, we screened oriental medicines to find M1 polarizing medicines in M2-polarized macrophages. Among approximately 400 types of oriental medicine, the ethanol extract of M. phalerata (EMP) was the most proficient in increasing TNF-α secretion in M2-polarized macrophages and TAM. Although EMP enhanced the levels of an M1 cytokine (TNF-α) and a marker (CD86), it significantly reduced the levels of an M2 marker (arginase-1) in M2-polarized macrophages. In addition, EMP-treated macrophages increased the levels of M1 markers (Inos and Tnf-α) and reduced those of the enhanced M2 markers (Fizz-1, Ym-1, and arginase-1). EMP-treated macrophages significantly reduced Lewis lung carcinoma cell migration in a transwell migration assay and inhibited EL4-luc2 lymphoma proliferation. In our mechanism study, EMP was found to inhibit STAT3 phosphorylation in M2-polarized macrophages. These results suggest that EMP is effective in treating TAM-mediated tumor progression and metastasis.

Highlights

Tumor burden comprises a group of heterogeneous cells, including T cells, neutrophils, and macrophages
M2 macrophages were induced by treating Bone marrow macrophages (BMM) with mouse recombinant IL-4 (20 ng/mL) and IL-13 (20 ng/mL) for 6 h, after which extract of M. phalerata (EMP) was added for 18 h
EMP enhances M1 cytokine (TNF-α) release and inhibits M2 cytokine (TGF-β) and M2 markersw such as YM1, Fizz1, and arginase-1 in M2 polarized macrophages by IL-4 and IL-13

Summary

Introduction

Tumor burden comprises a group of heterogeneous cells, including T cells, neutrophils, and macrophages. The major cells comprising the tumor burden are macrophages, accounting for approximately 50% of the burden. Tumorassociated macrophages (TAM) are involved in tumor progression and metastasis, and the number of TAM in the tumor burden is positively correlated with poor prognosis [1]. Macrophages can be M1 polarized by stimulation with IFNγ or LPS, and these M1-polarized macrophages secrete IL-12, TNF-α, and IL-1β, which kill cancer cells [2]. M2 macrophages are polarized by stimulation with IL-4, IL-13, or M-CSF and release IL-10, CCL17, and CCL22, which help in tumor progression and metastasis. Switching TAM or M2 with M1 is a potential target for cancer treatment

Methods

Results

Conclusion