Aflatoxin B1의 면역억제작용

문은이,이동권,표석능 성균관대학교 약학연구소 1996 成均藥硏論文集 Vol.8 No.1

Aflatoxin B1 (AFB1) has been reported to directly suppress the immune responses. In the present study, the effect of AFB1 on immune functions was investigated. Splenic lymphocytes were treated with various doses of the mitogens (lipopolysaccharide, concanavalin A) in the presence of AFB1. AFB1 pretretment decreased the number of plaque forming cells (PFC) in a dose-dependent manner. Antibody production of IgM and IgG class was significantly decreased in AFB1-treated splenic cells. In addition, when animals were exposed to AFB1, the susceptibility of bacterial infection as well as the growth of tumor cells was increased. These data suggest that AFB1 affected the immune function and humoral immunity impaired by AFB1 treatment contributed to pathological process.

Inducing apoptpsis by the inhibition of c-myb in oral squamous carcinoma cell line, KB cell

Lee,Jung-Chang 대한구강생물학회 2007 International Journal of Oral Biology Vol.32 No.4

Oral squamous cell carcinoma (OSCC) is the most commonmalignancy and is a major cause of worldwide cancer mortality.The proto-oncogene c-myb plays an important role in regulationof cell growth and differentiation, and it is expressed at highlevels in hematopoietic cells and many other types of cancers.However, the function of c-myb is not well known in OSCC.The present study aimed to reveal the function of c-myb and totest the alternation of cell growth and signaling by c-myb inOSCC. In this study, c-myb and dominant-negatibe myb(DN-myb) were expressed in an adenovirus-mediated gene deliverysystem to KB cells. The over-expressed c-myb broughtincreased cellular proliferation compared with control cells.However, DN-myb infected KB cells showed significantreduction of cell growth and enhanced induction of apoptosis toactivate PARP and caspase 9. c-myb induced increase of IGF-I,-II and IGF-IR expressions while DN-myb down-regulatedthese expression. Activation of ERK and Akt/PKB pathwaywas shown only in c-myb transduced cells. These findingssuggest that the role of c-myb in cell growth of oral cancer cellsis partially mediated through the modulation of IGFs, ERK andAkt/PKB. From this results, DN-myb is strongly recommendedas a curable gene for the treatment of c-myb dependentmalignancies such as OSCC.

소나무류 육종에 있어 임의 증폭 다형 디엔에이(RAPD)지표를 이용한 우량 임목의 조기 선발

로버트 티즈데일,이재선,정은주,문홍규,글렌 데일 江源大學校 林科大學 森林科學硏究所 1995 Journal of Forest Science Vol.11 No.-

지표-형질의 상관은 우량 개체 선발과 유전획득량의 증대를 위해 임목 육종에서 해결되어야 할 중요한 과제 중의 하나로 최근 분자유전학적 수준에서의 임의 증폭 다형 디엔에이 (RAPD) 기술의 발달로 이의 해결이 눈 앞에 다가왔다. 호주 퀸즈랜드산림청과 퀸즈랜드대 임목생물공학연구소가 공동 연구하고 있는 슬래쉬소나무, 카리비아소나무 및 그 교잡종에 있어 이 기술을 이용한 수피 두께에 대한 연구 및 육종 계획 전략을 소개한다. 1대 잡종에서 186개의 지표를 포함한 총 길이 1641cM의 16개 연관군의 유전적 지도가 작성되었고, 이 연관군 지도에 수피 두께를 지배하는 6개의 유전자좌가 추정되었다. 또한, 유전적 지표를 이용한 조기 선발을 위해 먼저 중요 형질을 지배하는 유전자들에 대한 종 특성 유전적 지표를 결정하고, 다음 여러가지 대립유전자형에 대한 지표-대립유전자 상관을 구명하는 2단계 전략이 제시되었다. 소나무류는 발아시 양료로 쓰이는 자성배우체는 모수에서 유래하나, 접합자인 배는 양친수로부터 유래하므로 이러한 이질적 유전 조성을 갖인 종자의 발달을 이용한 RAPD 지표와 형질의 상관 연구는 배 단계에서도 우량 개체의 선발을 가능하게 하여 소나무류 육종의 장래를 밝게 하고 있다. Random amplified polymorphic DNA (RAPD) technology, a recent approach in molecular genetics, is much usable to select the elite trees and to maximize the genetic gain in forest tree breeding program, providing a clue to determine the genetic marker-trait correlation. This review intorduces research on bark thickness and breeding strategy in Pinus elliottii, Pinus caribaea and their hybrid by Queensland Forest Service and ForBio Research Pty Ltd, University of Queensland, which employ RAPD technology. Genetic linkage map of F₁hybrids includes 186 RAPD markers and 16 linkgae groups (1641 cM long in total) and 6 quantitative trait loci are located putatively for bark thickness. Following recent research results and experiences in pine breeding programs, the forseeable stages in the application and development are proposed for marker assisted selectin; stage 1 - determination of species specific markers for genes controlling traits of commercial interest, and stage 2 - determination of marker-allele association for specific allelic variants within pure species. As pines inherit their megagametophytes from the seed parent and zygotic embryos from both male and female parents, the determination of marker-trait correlation is possible even in embryo stage, eventually making ways for the early selection of elite individuals.

Expansin으로 형질전환 된 담배의 생장 특성

신하정, 성현정, 백승준, 김보미, 엄유리, 조은정, 정찬문, 이이 충북대학교 연초연구소 2008 煙草硏究 Vol.21 No.-

-본문참고-

Immunomodulating Activity of DW-116, A New Quinolone Antibiotic

Moon, Eun-Yi,Choi, Chung-Ha,Pyo, Suh-Kneung,Chung, Yong-Ho,Yoon, Sung-June,Lee, Dug-Keun The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.5

DW-116, [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquino-line-3-carboxylic acid hydrochloride}, is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the immunomodulating activities, which is one of the efforts to investigate the mechanism of action related to the good in vivo antibacterial efficacy. The results of in vitro studies revealed there was no statistically significant increase in B and T lymphocyte proliferation. But the results of in vivo studies showed that the number of plaque forming cells (PFC), the amount of polyclonal antibodies and delayed-type hypersensitivity (DTH) were significantly increased after the repeat administration with 12 and 60 mg/kg of DW-116. Taken together, these results proposed that immunostimulting effect of DW-116 could be one of the action mechanisms for demonstrating in vivo antibacterial activities under these experimental conditions.

Effect of DW282 on the Induction of Methemoglobinemia, Hypoglycemia or WBC Count and Hematological Changes

Moon, Eun-Yi,Hwang, Hyun-Sook,Choi, Chung-Ha,Jung, Sang-Hun,Yoon, Sung-June The Pharmaceutical Society of Korea 1999 Archives of Pharmacal Research Vol.22 No.6

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl]-4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induced methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it dose produce.

AFLATOXIN B1-INDUCED SUPPRESSION OF NITRIC OXIDE PRODUCTION IN MURINE PERITONEAL MACROPHAGES

Moon, Eun Yi,Han, Jae Jin 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Aflatoxin B1 (AFB1), a potent hepatocarcinogen, is known to impair specific and nonspecific immune responses. AFB1 mainly decreases lymphocyte functions and may also affect macrophages assisting lymphocyte functions. Macrophages play an important role in a host defense against tumors and bacteria. Furthermore, some macrophage products, including nitric oxide (NO), may be involved in cytotoxicity. The effect of aflatoxin B1 (AFB1) was investigated on NO production from murine peritoneal macrophages. Macrophages were pretreated with AFB1 for 24h and then stimulated with lipopolysaccharide (LPS) for 24 h. AFB1 at 10 or 50 ㎛ reduced the production of NO. Compared to vehicle control, there was a greater reduction of NO production with increased AFB1 pretreatment and LPS stimulation. AFB1 at 10 or 50㎛ decreased inducible nitric oxide synthase (iNOS) activity about 24% and 28%, respectively, after stimulation with 1㎍/㎖ LPS and about 12% and 24%, respectively, after stimulation with 10㎍/㎖ LPS. AFB1 pretreatment also decreased the synthesis of iNOS protein and the mRNA of macrophages. Taken together, these results suggest that AFB1 pretreatment reduces NO production from murine peritoneal macrophages stimulated by LPS, which is mediated by the reduction of iNOS activity, mRNA, and protein.

An increase in mouse tumor growth by an <i>in vivo</i> immunomodulating effect of titanium dioxide nanoparticles

Moon, Eun-Yi,Yi, Geun-Hee,Kang, Jong-Soon,Lim, Jong-Seok,Kim, Hwan-Mook,Pyo, Suhkneung Informa Healthcare 2011 Journal of immunotoxicology Vol.8 No.1

<P>Here, we investigated whether titanium dioxide (TiO<SUB>2</SUB>) nanoparticles affect <I>in vivo</I> tumor growth through the modulation of mononuclear leukocytes. <I>In vitro</I> lymphocyte proliferation by lipopolysaccharide (LPS) or concanavalin A (ConA) was reduced by < 25 ??nm TiO<SUB>2</SUB> with a dose-dependent manner. Similarly, TiO<SUB>2</SUB> nanoparticles inhibited nitric oxide (NO) production from bone marrow-derived macrophages obtained from naï챦ve mice. When mice were intraperitoneally (IP) injected with < 25 or < 100 ??nm TiO<SUB>2</SUB> once a day for 7 days, total cell number of splenocytes was reduced in the spleen of TiO<SUB>2</SUB> nanoparticle-exposed mice. Both CD4<SUP>++</SUP> and CD8<SUP>++</SUP> T-lymphocyte numbers were significantly decreased and B-lymphocyte development was retarded by host exposure to the TiO<SUB>2</SUB> nanoparticles. LPS-stimulated spleen cell proliferation was significantly reduced by host exposure to < 25 or < 100 ??nm TiO<SUB>2</SUB>, but no changes were detected in ConA-stimulated spleen cell proliferation. Further, LPS-stimulated cytokine production by peritoneal macrophages and the percentage of NK1.1<SUP>++</SUP> natural killer cells among splenocytes was reduced by the host exposures to the TiO<SUB>2</SUB> nanoparticles. When mice were IP injected with TiO<SUB>2</SUB> nanoparticles once a day for 28 days prior to the subcutaneous implantation of B16F10 melanoma cells, tumor growth was subsequently significantly increased. Collectively, these results show that TiO<SUB>2</SUB> nanoparticles may damage the development and proliferation of B- and T-lymphocytes, reduce the activity of macrophages, and decrease natural killer (NK) cell population levels, outcomes that appear to lead to an increase in tumor growth <I>in situ</I>. These studies allow us to suggest that TiO<SUB>2</SUB> nanoparticles might have the potential to enhance tumor growth through immunomodulation of B- and T-lymphocytes, macrophages, and NK cells.</P>

In vitro suppressive effect of aflatoxin B_1 on murine peritoneal macrophage functions

Moon, Eun-Yi,Rhee, Dong-Kwon,Pyo, Suhkneung 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

We examined the immunosuppressive effects of aflatoxin B_1(AFB_1), a toxic compound produced by the Aspergillus Flacus, on murine peritoneal macrophages after in vitro pre-exposure. When thioglycollate-elicited macrophages pre-exposed to AFB_1 were stimulated with lipopolysaccharide (LPS), antitumor activity induced by LPS was suppressed by 10 and 50 μM AFB_1. In addition, the production of reactive intermediates including nitric oxide (NO), superoxide anion and hydrogen peroxide which have been known to be implicated in macrophage-mediated cytotoxicity, was decreased by AFB_1 pretreatment in a dose-dependent manner. We also determined whether the macrophage-mediated cytokine production was altered by AFB_1 in vitro pretreatment. AFB_1 markedly inhibited TNF-α, interleukin-1 (IL-1) and IL-6 production by LPS-stimulated macrophages. Taken together, these data indicate that AFB_1 inhibits the killing ability of murine macrophages, decreases various secretory molecules in those cells and the macrophages would be one of many systems affected by AFB_1. ⓒ 1999 Elsevier Science Ireland Ltd. All rights reserved.

Epac1-mediated Rap1 activation is not required for the production of nitric oxide in BV2, murine microglial cells

Moon, Eun-Yi,Oh, Su-Young,Han, Gyoon-Hee,Lee, Chul-Sang,Park, Song-Kyu Wiley Subscription Services, Inc., A Wiley Company 2005 JOURNAL OF NEUROSCIENCE RESEARCH - Vol.81 No.1

<P>This study demonstrates that cyclic AMP (cAMP) production is induced by lipopolysaccharide (LPS) stimulation and activates two different pathways in murine BV2 microglial cells. Two principal effector proteins for cAMP are protein kinase A (PKA) and cAMP-responsive guanine nucleotide exchange factor (Epac), a Rap GDP exchange factor. When cells were treated with various cAMP level modulators, nitric oxide (NO) production increased as the result of posttreatment with Type IV phosphodiesterase (PDE4) inhibitor, rolipram or dibutyryl-cAMP (dbcAMP), at 2 hr after LPS stimulation. Intracellular cAMP increased due to LPS stimulation and the cAMP modulators phosphorylate transcription factor CREB, which is enhanced in turn by posttreatment with dbcAMP. In contrast, the Epac-specific cAMP analog 8-(4-chloro-phenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8CPT-2Me-cAMP) activates Rap1 in the BV2 cells, but does not induce PKA activation, as judged by CREB phosphorylation. NO production was enhanced by posttreatment with dbcAMP but not by treatment with 8CPT-2Me-cAMP. This suggests that LPS-stimulated NO production is mainly PKA-dependent and also that Epac1-mediated Rap1 activation is not required for the induction of NO production. © 2005 Wiley-Liss, Inc.</P>