CD1d와 상호작용하는 단백질의 동정

황광우,전태훈,Hwang, Kwang-Woo,Chun, Tae-Hoon 대한약학회 2006 약학회지 Vol.50 No.4

CD1d is an unique antigen presenting molecule which provides antigenic repertoires to NKT cells. To examine molecules required for CD1d antigen presentation, we determined an interaction between CD1d and several endoplasmic reticulum (ER) resident molecular chaperones by co-immunoprecipitation. Results indicated that calnexin and calreticulin seem to be bound to mouse CD1d, but TAP and tapasin do not bind. Further, we screened an yeat two hybrid system to identify proteins that help mouse CD1d transportation in the cytosol. We found that two proteins, heat shock protein a sub-unit $(Hsp90{\alpha})$ and protein kinase C and casein kinase substrate in neurons 3 (PACSIN-3), interact with CD1d. Future study will be focus on the role of these molecules during the CD1d antigen presentation.

흰쥐 뇌 소교세포에서 진세노사이드 Rg3의 Type A Macrophage Scavenger Receptor 발현 증진효과

주성수,황광우,이도익,Joo, Seong-Soo,Hwang, Kwang-Woo,Lee, Do-Ik 대한약학회 2005 약학회지 Vol.49 No.2

Macrophage scavenger receptors (MSRs) induce microglial interaction with ${\beta}$-amyloid fibrils (fA${\beta}$) that are associated with Alzheimer's disease (AD). Although microglia are know n to have a dual effect on formation of plaque and clearance of fA${\beta}$ in the AD brain, receptor-mediated phagocytosis is a very important tool for preventing amyloid plaque via activated microglia in the early stage of AD. In the study, we examined whether ginsonoside Rg3 enhances the microglial Phagocytosis of A${\beta}$1-42 through Phagocytosis assay, gene expression (RT-PCR) and protein assay (western blots) for the cell responsiveness presented between Rg3-treated and non-treated groups. Fluro-labeled Ac-LDL and E.coli particles were used as control proteins for phagocytosis. In previous studies, this was a particularly interesting property of Rg3 in the stimulation and phagocytosis of macrophages in the periphery. We report here that ginsenoside Rg3 increased the expression of type-A MSR (MSR-A) in microglia and thus accelerated the phagocytosis with an effective degradation of engulfed fA${\beta}$. This result suggests that Rg3 may play an important role in removing fA${\beta}$ by enhancing the receptor-mediated phagocytosis. In addition, Rg3 could be a potential candidate for balancing the rate of production of fA${\beta}$ in AD brain.

마우스 간염바이러스(MHV-2)에 의해 유발된 전격성 바이러스간염에 대한 비페닐메칠디카르복실레이트/아만타딘제제의 간보호 및 잠재적 항바이러스효과

주성수,진혁준,원태준,장수길,황광우,이도익,Joo, Seong-Soo,Chin, Hyouk-Jun,Won, Tae-Joon,Jang, Su-Kil,Hwang, Kwang-Woo,Lee, Do-Ik 대한약학회 2007 약학회지 Vol.51 No.3

The mouse hepatitis virus (MHV-2) induces broad collapses, focal necrosis and cytolysis of hepatocytes, and leads to death after three to five days of intraperitoneal injection in mice. The present study investigated whether the combinatorial treatment of dimethyl dicarboxylate/amantadine (2:1) showed hepatoprotective and/or antiviral properties in MHV-2 infected ICR mice. In the study, we found that dimethyl dicarboxylate/amantadine group (VDDBA) increased the survival rate (30.8%) when compared to positive control, VL (7.7%) and that VDDBA lengthened the survival time (4.2 d)after MHV-2 infection. In addition, ALT and AST were well regulated when treated with VDDBA (p<0.01). Finally, we concluded that those results were probably from the inhibition of viral replication and at least antiproliferative effect on MHV-2.

간암세포주 HepG2 2.2.15에서 아만타딘/비페닐디메칠디카르복실레이트 복합제의 항 바이러스 효과

주성수,원태준,이용진,황광우,이도익,Joo, Seong-Soo,Won, Tae-Joon,Lee, Yong-Jin,Hwang, Kwang-Woo,Lee, Do-Ik 대한약학회 2005 약학회지 Vol.49 No.2

For decades, the demand for new antiviral strategies, especially in hepatitis, has increased markedly due to its devastating pathogenic outcome, In the present study, we examin ed the antiviral effect of the combination of amantadine and biphenyl dimethyl dicarboxylate (DDB) in HepG2 2.2.15, which is transfected with HBV DNA. The study demonstrated that the combination not the single treatment may have an anti-HBV effect through a synergism of antiviral, anti-inflammatory and cytoprotective activities in STAT1 ${\alpha}$, 6-16 gene, and pro-inflammatory components such as nitric oxide and IL-1${\beta}$ expression. In addition, hepatitis B surface and core gene expression were examined as a final end point for the anti-HBV activities, which was also significantly suppressed comparing to normal control (p<0.01).

해양칠게 혈림프로부터 렉틴의 분리 및 당 결합특성

김하나(Ha Na Kim),정우혁(Woo Hyuk Chung),배찬영(Chan Hyung Bae),황광우(Kwang Woo Hwang),김하형(HaHyung Kim) 대한약학회 2006 약학회지 Vol.50 No.3

A calcium-dependent sialic acid-binding lectin has been isolated by thyroglobulin-affinity chromatography from the coastal crab Macrophthalmus Japonicus. This lectin, Macrophthalmus Japonicus lectin (MJL), was eluted with 50mM Tris-HCl, 0.3M NaCl, 10mM EDTA, and the recovery yield from the crude protein extract was about 5.6%. The molecular weight of MJL was estimated as 65 kDa in SDS-PAGE both under reducing and non-reducing conditions. MJL induced an agglutination reaction in rabbit, rat, and mouse erythrocytes, but not in human ABO types. This activity was effectively inhibited by sialoglycoproteins such as fetuin, bovine submaxillary mucin, and thyroglobulin.

B 세포의 항체 생산에 대한 게란티 바이오-게르마늄 효모의 영향

주성수,원태준,이용진,김민정,박소영,이성희,이도익,황광우,Joo, Seong-Soo,Won, Tae-Joon,Lee, Yong-Jin,Kim, Min-Jung,Park, So-Young,Lee, Sung-Hee,Lee, Do-Ik,Hwang, Kwang-Woo 대한면역학회 2006 Immune Network Vol.6 No.2

Background: Germanium compounds are increased to use in nutrient foods and medicines in terms of antibiotics to microbes, anticancer, modulation of immune system and neutralizing heavy metal toxins. Geranti Bio-Ge Yeast, containing stable organic germanium and bound to the yeast protein was developed by Geranti Pharm. LTD. and the modulation effect in the immune system was examined in vivo and in vitro. Methods: The compound, Geranti Bio-Ge Yeast, was fed to female Balb/c mice (each group has 10 mice) for 4 weeks and the yeast powder and steamed red ginseng powder were used as control during the same feeding time points. During 4 weeks there was no symptom to be considered, and after 4 weeks feeding all mice were sacrificed to check the changes of related immune cells and subsidiary responses (i.e. cell counting, FACS, MTT, LDH, PFC assay). Results: In pre-post comparison, B cell population was increased in the group of Geranti Bio-Ge Yeast in a dose dependent manner (100 to 800 mg/kg). However, the population of T cell, dendritic cell and macrophage was not comparably changed in all doses. The ability of cytokine production and proliferation was almost same level as shown in control group. In contrast, PFC assay informed that the compound increase the antibody production ability when fed over 200 mg/kg implying that the increase of PFC number might be due to the increase of B cells. Conclusion: Over the entire study, we concluded that the compound, Geranti Bio-Ge Yeast has better potential in immune response in terms of B cell proliferation than that of positive control, red ginseng, and the compound can be one of the future candidates for a new supplementary source improving immune system activity.

오미자 활성성분 DDB의 NF-${\kappa}B$ 신호 전달 및 염증물질 발현 조절

주성수,유영민,원태준,김민정,이선구,황광우,이도익,Joo, Seong-Soo,Yoo, Yeong-Min,Won, Tae-Joon,Kim, Min-Jung,Lee, Seon-Goo,Hwang, Kwang-Woo,Lee, Do-Ik 대한면역학회 2006 Immune Network Vol.6 No.1

Background: Chronic inflammation in the brain has known to be associated with the development of a various neurological diseases including dementia. In general, the characteristic of neuro-inflammation is the activated microglia over the brain where the pathogenesis occurs. Pro-inflammatory repertoires, interleukin-1${\beta}$ (IL-1${\beta}$) and nitric oxide (NO), are the main causes of neuro-degenerative disease, particularly in Alzheimer's disease (AD) which is caused by neuronal destruction. Those pro-inflammatory repertoires may lead the brain to chronic inflammatory status, and thus we hypothesized that chronic inflammation would be inhibited when pro-inflammatory repertoires are to be well controlled by inactivating the signal transduction associated with inflammation. Methods: In the present study, we examined whether biphenyl dimethyl dicarboxylate (DDB), an active compound from Schizandra chinensis Baillon, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS) and IL-1${\beta}$. Western blots were also used for the analysis of NF-${\kappa}B$ and I${\kappa}B$. Results: In the study, we found that DDB effectively inhibited IL-1${\beta}$ as well as NO production in BV-2 microglial cell, and the translocation of NF-${\kappa}B$ was comparably inhibited in the presence of DDB comparing those to the positive control, lipopolysaccharide. Conclusion: The data suggested that the DDB from Schizandra chinensis Baillon may play an effective role in inhibiting the pro-inflammatory repertoires which may cause neurodegeneration and the results imply that the compound suppresses a cue signal of the microglial activation which can induce the brain pathogenesis such as Alzheimer's disease.

난소절제 랫드에서 회화나무 이소플라본의 갱년기증산 개선효과 및 신경세포 보호효과

주성수(Seong Soo Joo),원태준(Tae Joon Won),이용진(Yong Jin Lee),박소영(So Young Park),황광우(Kwang Woo Hwang),이도익(Do IK Lee) 대한약학회 2005 약학회지 Vol.49 No.4

Isoflavones are reported to play a role in menopausal women as a phytoestrogen, which can replace estradiols in hormone replacement therapy (HRT). Recently, due to the risk of breast cancer by HRT, phytoestrogens (e.g. isoflavones) have been focused as an alternative therapy in menopause. In the study, we investigated whether isoflavones derived from Sophorae fructus (SISO) have more benefit than that of soybean isoflavones in estrogen deficient rats. We found that SISO effectively controled H₂O₂ comparing with the baseline (p<0.01 vs. post value of OVX-Cont), and the blood sugar and weight were also controlled with decreasing patterns. Additionally, in LDH assay for cytoprotective effect in Neuro-2a cell line, SISO protected cells from the damage by SNAP (p <0.05). In conclusion, SISO may have more beneficial effect in enhancing the menopausal signs than that of soybean isoflavones and the cytoprotective effect in neuron cells suggests that SISO can play a certain role in neuroprotection after menopause.

대식세포의 Pro-inflammatory cytokine 생산에 대한 세포디짐의 효과

주성수,강희철,원태준,황광우,이도익 중앙대학교 약학연구소 2003 약학 논총 Vol.17 No.-

Cefodizime, a third cephalosporine, was originally developed for use in infectious disease as an advanced antibiotics. Cefodizime has also been known to play a meaningful role in activating natural killer properties of immune cells as well as enhancing immunological parameters such as phagocytosis. Furthermore, as the infection can result in remarkable changes for homeostatic mediators, it is expected that cefodizime may initiate the strong immuno- modualtory effect. In the present work, we investigated whether cefodizime has a biphasic effect of anti-bacteria and immunomodulation via macrophage. For the study, we isolated mouse peritoneal macrophages and treated with cefodizime 10㎍/㎖, 50㎍/㎖, 100㎍/㎖, IFN-v 10U/㎖.+LPS l㎍/㎖ Cells were then incubated for 4, 8, 12, and 24hrs to analysis the expression of IL-1, IL-6, IL-12 mRNA from macrophages. The results showed that cytokines were expressed more than that of control in a time-dependent manner and 100㎍/㎖ cefodizime group showed the greatest expression as much as the positive control (IFN-v+LPS)showed at 24h. In conclusion, cefodizime can play a significant role for the expression of pro-inflammatory cytokines, IL-1, IL-6, and IL-12 in earlier stage so that macrophages and other immune cells can response to the infectious substances, immediately. Moreover, when such pro-inflammatory cytokines are increased, we can also expect that the enhancement of cell-cell interaction of NK cell, CTL and B cell by cefodizime can affect the immunomodulatory effect along with its major role in anti-bacterial effect.