title: Macrophages Polarized by Expression of ToxoGRA15IIInhibit Growth of Hepatic Carcinoma.
abstract: A growing body of evidence suggests that tumor-associated macrophages are deeply involved in the hepatocellular carcinoma proliferation and account for the large proportion of infiltrated cells in tumor tissues and play a major role in promotion of tumor growth. On the other hand, studies have demonstrated thatToxoplasma gondiivirulence-associated molecule of dense granule protein (ToxoGRA15II) tends to induce classically activated macrophages (M1) differentiation. Thus, we explored the M1 induced by ToxoGRA15IIin vitroand its inhibitory impact on the proliferation, invasion, and metastasis of hepatic carcinoma in murine model. Here, we constructed recombinant plasmid ofpegfp-gra15IIand subsequently ligate it to lentivirus (Lv) vector, with which RAW264.7 was transfected. The results showed that the transfected macrophages were polarized to M1. Coculture of the M1 with Hepa1-6 cells showed a remarkable inhibition of migration and invasion of the tumor cells and decreased expressions of matrix metalloproteinase (MMP)-9 and MMP-2 without notable apoptosis of Hepa1-6 cells. Subsequently, ToxoGRA15II-polarized macrophages inoculated to tumor-bearing C57BL/6 mice were seen in both spleen and tumor tissues, and tumor growth was sharply restricted. Particularly, interleukin-6 (IL-6) expression, which is closely associated with the cancer malignant behaviors, was significantly dampened in tumor tissues. In addition, expression of TNF-α and IL-12 mRNAs was increased, whereas IL-6 and interleukin-10 mRNAs were downregulated in splenocytes. Our results indicate that the effector molecule of ToxoGRA15IImay induce macrophage polarization to M1 that has a restrictive effect on tumor growthviaits related cytokines profile in tumor and spleen tissues. Besides, ToxoGRA15II, due to its early activation of specified cell population and non-toxicity to mammalians, has a potential value for a novel therapeutic strategy of enhancing host innate immunity against tumor development.
authors.affiliation: Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University , Hefei , China.
authors.forename: Yuanling
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China; Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana.
authors.forename: Faustina
authors.initials: F
authors.lastname: Poppoe
authors.affiliation: Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University , Hefei , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University , Hefei , China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Laboratory Medicine, Provincial West Hospital, Anhui Medical University , Hefei , China.
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University , Hefei , China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Diagnostic Laboratory of the First Affiliated Hospital, Anhui Medical University , Hefei , China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Clinical Laboratory, Anhui Medical University , Hefei , China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China; Diagnostic Laboratory of the First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
keywords: Toxoplasma gondii; dense granule protein GRA15; hepatocellular carcinoma; polarization; tumor-associated macrophages