종양 미세 환경 내 대식세포에서 혈관 신생 조절 인자로서의 TNF-α에 의한 IFN-γ의 분비 조절

표석능,백소영,곽장동,박대섭,조성준,이현아,Pyo, Suhk-Neung,Baek, Soyoung,Kwak, Jang-Dong,Park, Dae-Sub,Joe, Sung-Jun,Lee, Hyun Ah 대한면역학회 2003 Immune Network Vol.3 No.1

Background: The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-${\alpha}$. Recently, macrophage also can produce the INF-${\gamma}$ that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-${\alpha}$ can modulate the INF-${\gamma}$ production in the macrophages from tumor environment as a part of tumor angiogenic switch. Methods: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. $Mac1^+$-macrophages were purified using magnetic bead ($MACs^{TM}$; Milteny Biotech, Germany) and cultured with various concentrations of TNF-${\alpha}$ for various time points at $37^{\circ}C$. The supernatants were analyzed for IFN-${\gamma}$ or VEGF by ELISA kit (Endogen, Woburn, MA). Results: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-${\alpha}$ to produce INF-${\gamma}$. However, the cells from tumor environment produced IFN-${\gamma}$ as well as VEGF and upregulated by the addition of LPS or TNF-${\alpha}$. RT-PCR analysis revealed the external TNF-${\alpha}$-induced IFN-${\gamma}$ gene expression in the macrophages from tumor environment. Conclusion: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-${\alpha}$ might be a key cytokine in tumor angiogenic switch.

면역보조제의 작용 및 개발

표석능,손은수,손은화 대한면역학회 2004 Immune Network Vol.4 No.3

In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology. (Immune Network 2004;4(3):131-142)

Double-stranded RNA의 치료효과

표석능 성균관대학교 약학연구소 1993 成均藥硏論文集 Vol.5 No.1

The synthetic, double-stranded RNAs including polyriboinosinic: polyribocytidylic acid (poly I : C)exert a wide diversity of biologic effects which has been shown at both the cellular and organism levels. Poly I : C is effective in vitro in inducing resistance to virus infection in a variety of cell types and in activating the cytotoxic potential of macrophages. In addition, poly I : C is a potent macrophage or NK cell activator and interferon inducer, which is effective in the prophylactic and therapeutic treatment of viral infections and in the therapy of tumor. Thus synthetic ds RNA can be utilized as a therapeutic agent, either alone or in combination with interferon.

대식세포에서 국산약용식물의 항암 및 항Virus 에 대한 효과

표석능(Suhkneung Pyo),지옥표(Ok Pyo Zee),엄성희(Sung Hee Um),김대근(Dae Keun Kim),곽종환(Jong Whan Kwak),이강노(Kang Ro Lee),이동권(Dong Kwon Rhee) 한국생약학회 1995 생약학회지 Vol.26 No.3

In the present work, 70 extracts from 23 plants have been determined to induce cytotoxic and antiviral activities of macrophages using both MTT assay and neutral red dye uptake assay. We show that 13 extracts have induced cytotoxic activities and 5 extracts induced antiviral activity in mouse peritoneal macrophages. Among 13 extracts, macrophages treated with extracts from Salvia plebeia have demonstrated significant cytotoxicity but not antiviral activity. The present findings indicate that extracts from plants can stimulate macrophages to become resistant to virus and to kill tumor cells.

Immunomodulatory effects of Red ginseng acidic polysaccharide (RGAP) and non­saponin red ginseng components (NSRG) on innate immune cells

Suhkneung Pyo(표석능) 고려인삼학회 2009 고려인삼학회 학술대회 Vol.2009 No.12

The Mechanisms of Interferon-α and Interferon-γ Induced Antiviral Activity in Peritoneal Macrophages

Pyo, Suhkneung,Lee, Jae-Hag,Rhee, Dong-Kwon 성균관대학교 약학연구소 1997 成均藥硏論文集 Vol.9 No.1

대식세포는 세포 내에서 바이러스복제를 억제함으로서 바이러스 감염에 대한 숙주반응에서 중요한 역할을 한다. 인터페론은 바이러스 감염시 세포가 분비하는 항바이러스 효과를 갖고 있는 단백질로서 인터페론 생성을 유도하는 poly I : C와 같이 대식세포에서 다른 인터페론을 유도하여 항바이러스작용을 나타낼 가능성이 있기 때문에 인터페론에 의해 활성화된 대식세포가 HSV-1의 감염에 대한 저항작용기전을 연구하였다. 대식세포를 인터페론-α 또는 인터페론-γ 및 인터페론 항체를 함께 처리하여 HSV-1감염에 대하여 저항하는 대식세포의 능력을 평가하였다. 인터페론 항체는 HSV-1에 감염된 대식세포에서 인터페론의 보호효과를 중화시키지 못하였다. 또한 인터페론을 처리한 대식세포의 상층액에서 인터페론을 탐지할 수 없었다. 이는 poly I : C가 인터페론-β 생성을 유도하여 항바이러스효과를 나타내는 작용기전 (Pyo et al. J. Leukocyte Biol. 50:479)과는 달리 인터페론-α와 인터페론-γ는 인터페론-β 생성과정을 경유하지 않고 직접적으로 대식세포에 작용하여 항바이러스 효과를 나타내는 듯하다.

RNA and protein synthesis requirement for poly I:C-induced antiviral activity in peritoneal macrophages

Pyo, Suhkneung,Rhee, Dong-Kwon 성균관대학교 약학연구소 1995 成均藥硏論文集 Vol.7 No.1

Abstract - Poly I:C에 의해 유도된 대식세포의 항바이러스 작용에 RNA 또는 단백질 합성이 필요한지를 결정하였다. Actinomycin D 또는 cycloheximide로 대식세포를 전처리 하였을 때 poly I:C의 항바이러스 효과가 감소되었으나 actinomycin D 또는 cycloheximide를 후처리하였을 때는 억제되지않아 poly I:C의 항바이러스 작용에 RNA와 단백질 합성이 요구되는 듯 하며 poly I:C 처리의 초기단계에서 interferon이 생성되는 듯하다.

Inhibitory Effects of Allicin on TNF-α-induced ICAM-1 Expression is Associated with Catalase

강남성,표석능,손은화 한국자원식물학회 2009 한국자원식물학회지 Vol.22 No.6

Allicin, a garlic componente, is believed to provide protection against various diseases including inflammation. Since interactions of the cell adhesion molecules are known to play important roles in mediating inflammation, inhibiting adhesion protein upregulation is a possible therapeutic target. In this study, we demonstrate that TNF-α- and catalase-induced expression of ICAM-1 on human lung epithelial cells (A549) in a dose-dependent manner and catalase expression and activity were also increased in TNF-α-treated cells. Treatment of the TNF-α-treated cells with catalase inhibitor 3-amino-1,2,4-triazole resulted in a significant decreased the level of ICAM-1. These data suggest that induction of ICAM-1 expression by TNF-α is associated with catalase. In addition, allicin was found to inhibit the TNF-α induced expression of ICAM-1 on the A549 cells. This compound also inhibited the production of catalase induced by TNF-α, which suggests that the inhibition of ICAM-1 expression by allicin may be due to the modulated production of catalase.

Immunomodulatory Effects of Cimicifugae Rhizoma Extracts in Macrophages

손은화,표석능,김병오,최혜숙 한국식품영양과학회 2006 Preventive Nutrition and Food Science Vol.11 No.4

Cimicifugae Rhizoma (CR) belongs to the Ranunculaceae family, which has been traditionally used to treat climacteric complaints, antipyretics and diaphoresis as an alternative medicine for estrogen hormone replacement therapy with estrogens. Recently, it has been reported that different extract fractions of CR have various effects such as anti-allergic, anti-inflammatory and anti-proliferative activities. The current study investigated the immunomodulatory effects of Cimicifugae Rhizoma water extracts (CRE) in the macrophage-like cell line, Raw 264.7. Our results showed that CRE (1~50 μg/mL) stimulated tumoricidal activity and NO production, whereas phagocytic activity was inhibited at the same concentrations. Additionally, iNOS mRNA expression was significantly increased in Raw 264.7 exposed to CRE as demonstrated by RT-PCR. These results indicate that the tumoricidal activity induced by CRE may be mediated by the production of NO and these activities may be useful for the treatment of diseases such as cancer.

폐렴구군 Type 23 협막다당류 생산의 최적화

민관기,표석능,이동권 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

Abstract-Streptococcus pneumoniae (pneumococcus) is the most frequent causative agent of acute bacterial pneumonia. Outstanding characteristic of pneumococcus is an ample polysaccharide capsule that is highly antigenic agent and is the major factor for classification of pneumococcus into more than 94 serotypes. In this study, production of capsular polysaccharide from Streptococcus pneumoniae type 23 was optimized by supplementation of metal ions or by modulation of culture conditions. When brain heart infusion (BHI) broth was supplemented with 1 mM concentration of CaCl_2, CuSO_4 and MgSO_4, growth of pneumococcus as well as polysaccharide yield were stimulated. Also slight aeration gave rise to better polysaccharide yield.