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.
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.
Yang
Xin-Ying
XY
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, South Korea.
Cai
Sheng-Xin
SX
Zhang
Wen-Ji
WJ
Tang
Xue-Lian
XL
Shin
Hye-Young
HY
Lee
Joo-Young
JY
Gu
Qian-Qun
QQ
Park
Hyun
H
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics*; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009284:Naphthols / Q000302:isolation & purification / Q000494:pharmacology*; D011753:Pyrones / Q000302:isolation & purification / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016328:NF-kappa B; D009284:Naphthols; D011753:Pyrones; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; C432929:semivioxanthin; D020928:Mitogen-Activated Protein Kinases