SJSZ glycoprotein (38 kDa) modulates macrophage type 1/2-related factors at hepatocarcinogenic stage in N-nitrosodiethylamine-treated Balb/c.

Macrophage plays critical role for tumor progression: Type 1 (M1) for tumor prevention and type 2 (M2) for promotion in hepatocellular carcinoma. In order to study the chemopreventive effects of the SJSZ glycoprotein (38 kDa) on M1- or M2-related factors, Balb/c was injected intraperitoneally with N-nitrosodiethylamine (DEN; 50 mg/kg, BW) for 7 weeks. After 7 weeks, the mice were sacrificed. After that, peritoneal macrophages were isolated. We evaluated the production of reactive oxygen species (ROS) and nitric oxide (NO), hepatocarcinogenic signals [activities of mitogen-activated associated kinase (MAPKs), inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, and signal transducer and activator of transcription (STAT) 6,], cytokines [interleukin (IL)-10, IL-4, IL-12, and interferon (IFN)-γ], and CD163-positive macrophages (M2 polarization) using biochemical methods, immunoblot analysis, qRT-PCR, ELISA, and flow cytometry. The results revealed that the SJSZ glycoprotein (10 mg/kg, BW) inhibits the phosphorylation of MAPKs and expression of NF-κB, pSTAT6, IL-10, and IL-4; and normalizes production of ROS and NO, and expression of iNOS, IL-12, and IFN-γ. Especially, it inhibited CD163-positive macrophages. In conclusion, these results indicated that SJSZ glycoprotein modulates polarization of macrophage type 1 and type 2 at hepatocarcinogenic initial stage in DEN-treated Balb/c. Thus, SJSZ glycoprotein may be useful as one of immunomodulating agents which have to regulate M1- and M2-related factors to prevent tumor progression.