Effect of silkworm peptide on inducting M1 type polarization and Th1 activation via TLR2-induced MyD88-dependent pathway.

Zhongzheng Gui,Guanglai Zhu

doi:10.1002/fsn3.954

Abstract

The aim of this study was to explore immune activity and molecular mechanism of silkworm peptide. The cell subsets induced by silkworm peptides were detected by flow cytometry. The IFN‐γ and IL‐4 levels in CD4+ cells were measured by ELISA. TLR2 mRNA expression in mouse CD4+ T cells was detected by qRT‐PCR. Western blot was used to detect the protein expression levels of MyD88 and p‐IκB. The growth rate of Lewis lung cancer xenografts in mice of the medium‐dose group was significantly reduced, and the tumor volume was significantly smaller than that of the control group on the 14th day. The relative vitality values of spleen lymphocytes in the medium‐dose and high‐dose groups were higher than the control group. The IFN‐γ levels in the medium‐dose and high‐dose groups were significantly higher than the control group. The levels of IL‐4 were no significant change among different groups. Compared with the control group, different doses of silkworm peptide groups could increase the levels of NO, IL‐6, IL‐12, and IL‐1β. Compared with the control group, the protein expression levels of MyD88 and p‐IκB in 10 μg/ml group and 20 μg/ml groups were significantly increased compared with the control group. Silkworm peptide could induce Th1 activation and M1 type polarization, which was dose‐dependent and was relative to the effect of silkworm peptide on inhibiting tumor growth. Silkworm peptide could directly induce M1 type polarization and Th1 activation via TLR2‐induced MyD88‐dependent pathway in vitro.

Highlights

Lung cancer causes an estimated 1.6 million deaths each year, being the leading cause of cancer‐related deaths in the world (Ostrowski, Marjański, & Rzyman, 2018)
The above results suggested that the silkworm peptide could significantly inhibit the growth of Lewis lung cancer xenografts, and the effect was in a concentration‐dependent manner
The above experimental results suggested that silkworm peptide could significantly increase the phagocytic activity of peritoneal macrophages in Lewis lung cancer model mice, and the effect was in a concentration‐dependent manner

Summary

Introduction

Lung cancer causes an estimated 1.6 million deaths each year, being the leading cause of cancer‐related deaths in the world (Ostrowski, Marjański, & Rzyman, 2018). ZHU and GUI become a new research hot spot It can enhance the immune function of the patient's body, exert an antitumor effect, and improve the tumor treatment effect (Reck, 2017; Wu, Kao, & Lai, 2018). Macrophages mainly differentiate into M1 and M2, and play different roles in tumor development (den Breems & Eftimie, 2016). Studies have found that CD4+ T cells can be divided into two cell subpopulations, Th1 cells and Th2 cells, which play different roles in the development of tumors (Hirahara & Nakayama, 2016; Tsuda et al, 2017). Th1 cells mainly secrete cytokines such as IFN‐γ, IL‐12, and TNF‐α, which have significant anti‐intracellular bacteria, viral infections, and antiviral effects (Hwang, Kim, Lee, & Lee, 2012; Soleimani, Jameie, Barati, Mehdizadeh, & Kerdari, 2014)

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Conclusion