Semi-vioxanthin isolated from marine-derived fungus regulates tumor necrosis factor-alpha, cluster of differentiation (CD) 80, CD86, and major histocompatibility complex class II expression in RAW264.7 cells via nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways

• Published in: Biological & pharmaceutical bulletin 2008, Vol.31 (12), p.2228-2233
• Main Authors: Yang, Xin-Ying, Cai, Sheng-Xin, Zhang, Wen-Ji, Tang, Xue-Lian, Shin, Hye-Young, Lee, Joo-Young, Gu, Qian-Qun, Park, Hyun
• Format: Article
• Language: English
• Subjects: Animals; B7-1 Antigen - biosynthesis; B7-1 Antigen - genetics; B7-2 Antigen - biosynthesis; B7-2 Antigen - genetics; Blotting, Western; Cell Line; Electrophoretic Mobility Shift Assay; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression - drug effects; Genes, MHC Class II - genetics; Macrophages - drug effects; Macrophages - metabolism; Macrophages - physiology; Mice; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - physiology; Naphthols - isolation & purification; Naphthols - pharmacology; NF-kappa B - genetics; NF-kappa B - physiology; Pyrones - isolation & purification; Pyrones - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - genetics; Signal Transduction - physiology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Up-Regulation - drug effects
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.2228

Semi-vioxanthin isolated from marine-derived fungus was assessed for immunoregulatory activity in mouse RAW264.7 macrophages. In the present study, the facilitative effects of semi-vioxanthin on tumor necrosis factor-alpha (TNF-alpha) and its mRNA expression and on expression of the co-stimulatory molecules, cluster of differentiation (CD) 80, CD86 and major histocompatibility complex class II (MHC II), as well as the molecular mechanism underlying the immunologic enhancement properties of semi-vioxanthin were studied. Our results clearly indicated that semi-vioxanthin treatment resulted in the degradation of IkappaB alpha, which led to the activation and nuclear translocation of the p65 subunit of nuclear factor-kappaB (NF-kappaB), as determined by immunoblotting, immunofluorescence and electrophoretic mobility shift assays (EMSA). Moreover, TNF-alpha production was prevented by NF-kappaB and mitogen-activated protein kinase (MAPK) inhibitors. Inhibition of NF-kappaB and extracellular signal regulated kinases (ERK1/2) activity by specific inhibitors blunted the effect of semi-vioxanthin on the up-regulation of CD80, CD86 and MHCII expression, but neither p38 MAPK nor c-Jun N-terminal kinase (JNK) inhibitor had this effect. Thus, we demonstrate that semi-vioxanthin regulates TNF-alpha production through NF-kappaB and MAPK signaling pathways. Activation of NF-kappaB and ERK1/2 were necessary for CD80, CD86 and MHCII expression induced by semi-vioxanthin. These data suggest that semi-vioxanthin has immunoregulatory effects.