title: SJSZ glycoprotein (38 kDa) modulates macrophage type 1/2-related factors at hepatocarcinogenic stage in N-nitrosodiethylamine-treated Balb/c.
abstract: 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.
authors.affiliation: Molecular Biochemistry Laboratory, Biotechnology Research Institute & Center for the Control of Animal Hazards Using Biotechnology (BK21), Chonnam National University, 300 Yongbong-Dong, Gwang-ju 500-757, South Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Kye-Taek
authors.initials: KT
authors.lastname: Lim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000517:prevention & control*; D004052:Diethylnitrosamine; D006023:Glycoproteins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D010940:Plant Proteins / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D032362:Styrax / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006023:Glycoproteins; C556062:IL10 protein, mouse; D016328:NF-kappa B; D010936:Plant Extracts; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D009569:Nitric Oxide; D004052:Diethylnitrosamine; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020928:Mitogen-Activated Protein Kinases