Myung-Woo Byun

Enhancement of anti-tumor activity of gamma-irradiated silk fibroin via immunomodulatory effects.

Silk fibers have proven to be effective in many clinical applications as well as for clothing. In addition to the substantial effect of silk fibers, the present study was conducted to explore its importance in a new dimension to reinforce the effects of its physiological function regarding anti-tumor activity and immune response with gamma-irradiated silk fibroin (GISF). The cytotoxicity results showed that pre-treatment of GISF in the mouse peritoneal macrophages (MPM) indicated a higher proliferative effect than that of non-irradiated silk fibroin (NISF) in a concentration-dependent manner. Based on the cytotoxicity result of MPM, GISF (50 and 150 kGy) was selected for an ex vivo study in an animal (C57BL6) system and evaluated about whether the non-specific immune response was also related to GISF. GISF (50 and 150 kGy) augmented immune responsiveness via activation of NK cells, T lymphocytes proliferation, NO production, and cytokine level, such as IL-6, IL-2, IL-12, IFN-gamma, TNF-alpha, as compared with NISF, which strongly suggested that GISF significantly augmented an important element of all aspects of the innate and adaptive immune system. Therefore, from these results, it seems likely that the GISF will play a potent role in eliciting the effect of the non-specific immune response and anti-tumor activity as a value-added product in the medical industry.

The procyanidin trimer C1 inhibits LPS-induced MAPK and NF-κB signaling through TLR4 in macrophages

Natural products and dietary components rich in polyphenols have been shown to reduce inflammation; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. This research was carried out to clarify the potential role of procyanidin trimer C1 in the anti-inflammatory effect of polyphenols. Procyanidin C1 inhibited inducible nitric oxide synthase-mediated nitric oxide production and the release of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) in lipopolysaccharide (LPS)-induced macrophages. Treatment with procyanidin C1 resulted in a significant decrease in prostaglandin E2 and cyclooxygenase-2 levels, as well as the expression of cell surface molecules (CD80, CD86, and MHC class II), which was induced by LPS. Furthermore, our data demonstrated that the anti-inflammatory effect of procyanidin C1 occurs through inhibition of mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase) and nuclear factor-κB signaling pathways. These 2 factors play a major role in controlling inflammation, through toll-like receptor 4, suggesting that procyanidin C1 plays a potent role in promoting anti-inflammatory activity in macrophages. These results represent a novel and effective therapeutic intervention for the treatment of inflammatory disease.

Biological evaluation of isoegomaketone isolated from Perilla frutescens and its synthetic derivatives as anti-inflammatory agents

The anti-inflammatory activities of a prepared isoegomaketone 3a and its derivatives 3b–3f were evaluated in RAW 264.7 cells. Among these, the compound 3d was displayed the most potent inhibitory activities against production of nitric oxide, monocyte chemoattractant protein-1 and interleukin-6. Based on these results, the abilities of compounds 3a–3f to modulate NF-κB and AP-1-mediated gene transcription using a luciferase reporter assay were investigated. The transcriptional activities of NF-κB and AP-1 decreased when pretreated with 3a–3f. Interestingly, at 10 μM, compound 3d markedly suppressed the lipopolysaccharide-induced NF-κB and activator protein-1 DNA binding activities. Some preliminary structure-activity relationships were proposed that may provide a direction for further study.

Effect of gamma irradiation on mistletoe (Viscum album) lectin-mediated toxicity and immunomodulatory activity

This study evaluated the effect of gamma irradiation on the reduction of the toxicity of mistletoe lectin using both in vitro and in vivo models. To extract the lectin from mistletoe, an (NH4)2SO4 precipitation method was employed and the precipitant purified using a Sepharose 4B column to obtain the pure lectin fraction. Purified lectin was then gamma‐irradiated at doses of 0, 5, 10, 15, and 20 kGy, or heated at 100 °C for 30 min. Toxic effects of non‐irradiated, irradiated, and heat‐treated lectins were tested using hemagglutination assays, cytotoxicity assays, hepatotoxicity, and a mouse survival test and immunological response was tested using cytokine production activity. Hemagglutination of lectin was remarkably decreased (P < 0.05) by irradiation at doses exceeding 10 kGy and with heat treatment. However, lectin irradiated with 5 kGy maintained its hemagglutination activity. The cytotoxicity of lectin was decreased by irradiation at doses over 5 kGy and with heat treatment. In experiments using mouse model, glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels were decreased in the group treated with the 5 kGy irradiated and heat‐treated lectins as compared to the intact lectin, and it was also shown that 5 kGy irradiated and heat‐treated lectins did not cause damage in liver tissue or mortality. In the result of immunological response, tumor necrosis factor (TNF‐α) and interleukin (IL‐6) levels were significantly (P < 0.05) increased in the 5 kGy gamma‐irradiated lectin treated group. These results indicate that 5 kGy irradiated lectin still maintained the immunological response with reduction of toxicity. Therefore, gamma‐irradiation may be an effective method for reducing the toxicity of lectin maintaining the immune response.

Induction of apoptosis by Myagropsis myagroides extracts is associated with a caspase dependent pathway and reactive oxygen species generation in human cancer cells

The purpose of this study was to elucidate the mechanisms underlying apoptosis induced by an ethanol extracts from Myagropsis myagroides (ME) in HeLa, U937, and PC-3 cells. ME treatment for 24 h significantly inhibited cell viability in a dose-dependent manner, and induced apoptosis. Moreover, ME treatment triggered the cleavage of caspase-8, −9, −3, and poly(ADP-ribose) polymerase (PARP). A general caspase inhibitor (z-VAD-fmk) inhibited ME-induced activation of caspase-3, PARP cleavage, and cell death. ME treatment also triggered the release of cytochrome c from the mitochondria to the cytosol and stimulated the cleavage of Bid, up-regulation of Bax, and down-regulation of Bcl-2. Furthermore, ME treatment caused reactive oxygen species (ROS) generation. An antioxidant N-acetylcysteine (NAC) blocked MEinduced activation of caspase-3, PARP cleavage, and cell death. Overall, these results suggest that ME-induced apoptosis is mediated by a caspase dependent pathway and ROS generation in HeLa, U937, and PC-3 cells.

Polysaccharide extracted from Sargassum fulvellum leads to macrophage activation and Th1 polarization in splenocytes

Marine organisms are a rich source of structurally diverse bioactive compounds that play a vital role in human health and nutrition. This study examined the immunomodulatory activities of polysaccharide extracted from Sargassum fulvellum in RAW264.7 macrophages and mice splenocytes. S. fulvellum polysaccharide extract (SPE) was obtained by ethanol precipitation after hot water extraction for 2xa0h. SPE treatment in macrophage cells did not induce cytotoxicity, but increased the levels of nitric oxide (NO) and cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-12p70), except for IL-10, that mediate immune suppression. Treatment also significantly increased the macrophage surface activation markers CD80 and CD86. Additionally, macrophage activation by SPE treatment modulated mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling. In splenocytes, SPE treatment markedly increased cell proliferation and Th1 cytokines (interferon [IFN]-γ), but did not increase Th2 cytokines (IL-4). Taken together, these results suggest that polysaccharide extracted from S. fulvellum could potentially be used as an immunomodulatory agent.