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배양심근세포의 산화적 손상에 대한 사물탕의 방어효과 (Protective Effects of Samul-tang on Oxidative Stress induced Death of H9c2 Cardioblast Cells)

  • 조권일;정승원;장재호;이대용;박세욱;이인;신선호;문병순
    • 대한한의학회지
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    • 제26권1호
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    • pp.174-186
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    • 2005
  • Objectives : The water extract of Samul-tang (SMT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of SMT rescues cells from these damages. Methods: This study was designed to investigate the protective mechanisms of SMT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Treatment with $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. Results: The characteristics of H20z-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation and morphological change. However, SMT significantly reduced both H202-induced cell death and morphological change. The decrease of Bc-2 expression by High were inhibited by SMT. In addition, the increase of Bax expression was also inhibited by SMT. The cotreatment of SMT and $H_2O_2$ in H9c2 cells also induced the phosphorylation of ERK in a time-dependent manner. Moreover, PD98059, a specific inhibitor of ERK1/2 attenuated the protective effects of SMT on $H_2O_2-induced$ toxicity in H9c2 cardiomyoblast cells. These results suggest that both ERK1/2 signaling pathways play important roles in the protective effects of SMT on $H_2O_2-induced$ apoptotic death of H9c2 cells. Also, the expression profile of proteins in $H_2O_2$ cardiomyoblast cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels, the comparison of control versus apoptosis cells revealed that signal intensity of 17 spots increased and 11 spots decreased. Conclusions: Taken together, this study suggests that the protectiw effects of the water extract of SMT against oxidative damages may be mediated by the modulation of Bc1-2 and Bax expression via the regulation of the ERK signaling pathway.

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한국인에서 치주질환과 관상동맥질환의 관련성에 대한 염증표지자와 IL-1 유전자 다변성의 영향 (Association between Periodontitis and Coronary heart disease in Korea : Inflammatory markers and IL-1 gene polymorphism)

  • 정하나;정현주;김옥수;김영준;김주한;고정태
    • Journal of Periodontal and Implant Science
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    • 제34권3호
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    • pp.607-622
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    • 2004
  • Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.

신(新) 유사정적 사면안정해석 기법 개발 (Development of Novel Method of Seismic Slope Stability Analysis)

  • 윤세웅;박두희;이승호;황영철
    • 한국지반환경공학회 논문집
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    • 제10권1호
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    • pp.49-54
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    • 2009
  • 지진동에 대한 사면의 안정성은 일반적으로 지진계수를 이용하여 지진하중을 유사정적 하중으로 단순화하여 한계평형법으로 평가된다. Transient 지진동은 지진계수를 이용하여 정적하중으로 대체된다. 하지만, 유사정적 해석결과에 절대적인 영향을 미치는 지진계수는 합리적인 물리적 근거 없이 산정된다. 또한 내진설계기준에 의거하여 산정되는 최대가속도는 사면의 진동특성을 반영한다고 볼 수 없으며, 이를 정확하게 예측하기 위해서는 2차원 동적해석을 수행해야 한다. 본 연구에서는 수정된 1차원 동적해석과 유사정적해석을 연결한 Hybrid 유사정적 해석법을 제안하였다. 기존의 해석기법은 깊이에 따라서 변이하는 가속도를 고려할 수 없기에 신뢰성 있는 사면의 안정성 예측이 어려운 실정이다. 수정된 1차원 지반응답해석은 깊이에 따른 사면 무게변화를 모델링하기 위하여 층의 밀도를 조정하였으며 위치별 진동가속도를 예측하기 위해서 다수의 해석을 수행하였다. 2차원 유한요소해석과 비교한 결과, 수정된 1차원 해석은 2차원 해석과 일치성이 우수한 것을 확인할 수 있었다. 해석결과를 유사정적해석에 입력하여 깊이에 따라서 변이하는 가속도 주상도를 적용하였으며 기존의 해석방법으로 계산된 안전율과 비교하였다. 비교 결과, 계산된 안전율에는 큰 차이가 발생하는 것으로 나타났으며, 기존의 해석기법으로 안전율을 예측할 경우, 매우 비현실적인 값을 계산할 수 있다. 본 연구에서 개발된 기법은 해석의 신뢰성을 현격하게 향상시키는 것으로 나타났다.

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SB202190- and SB203580-Sensitive p38 Mitogen-Activated Protein Kinase Positively Regulates Heat Shock- and Amino Acid Analog-Induced Heat Shock Protein Expression

  • Kim, Sun-Hee;Han, Song-Iy;Oh, Su-Young;Seo, Myoung-Suk;Park, Hye-Gyeong;Kang, Ho-Sung
    • 대한의생명과학회지
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    • 제9권2호
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    • pp.59-65
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    • 2003
  • When cells are exposed to proteotoxic stresses such as heat shock, amino acid analogs, and heavy metals, they increase the synthesis of the heat shock proteins (HSPs) by activating the heat shock transcription factor 1 (HSF1), whose activity is controlled via multiple steps including homotrimerization, nuclear translocation, DNA binding, and hyperphosphorylation. Under unstressed conditions, the HSF1 activity is repressed through its constitutive phosphorylation by glycogen synthase kinase 3$\beta$ (GSK3$\beta$), extracellular regulated kinase 1/2 (ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). However, the protein kinase (s) responsible for HSF1 hyperphosphorylation and activation is not yet identified. In the present study, we observed that profile of p38 mitogen-activated protein kinase (p38MAPK) activation in response to heat shock was very similar to those of HSF1 hyperphosphorylation and nuclear translocation. Therefore, we investigated whether p38MAPK is involved in the heat shock-induced HSF1 activation and HSP expression. Here we show that the p38MAPK inhibitors, SB202190 and SB203580, but not other inhibitors including the MEK1/2 inhibitor PD98059 and the PI3-K inhibitor LY294002 and wortmannin, suppress HSF1 hyperphosphorylation in response to heat shock and L-azetidine 2-carboxylic acid (Azc), but not to heavy metals. Furthermore, heat shock-induced HSF1-DNA binding and HSP72 expression was specifically prevented by the p38MAPK inhibitors, but not by the MEK1/2 inhibitor and the PI3-K inhibitors. These results suggest that SB202190- and SB203580-sensitive p38MAPK may positively regulate HSP gene regulation in response to heat shock and amino acid analogs.

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두부외상 환자의 신경정신의학적 평가(II) : 뇌의 구조적 영상검사상의 병변 유무에 따른 두부외상 환자군의 비교 - 기능적 및 심리적 검사소견과의 연관성을 중심으로 (Neuropsychiatric Evaluation of Head-Injured Patients(II) : A Comparative Study of Brain-injured Patients with and without Abnormal Findings in the Structural Brain Imaging - Mainly in Relation to Functional Brain Studies and Psychological Evaluation)

  • 조성욱;장환일
    • 생물정신의학
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    • 제3권1호
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    • pp.66-74
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    • 1996
  • There has been an increase in head trauma due to rapid industralization and improvement in transportation. This poses difficulties in differentiating between neuropsychiatric disabilities resulting from real organic changes and those arising from compensation issues. It is the purpose of this study to seek out the differences between normal and abnormal finding group in the structural brain imaging studies via the results of the functional brain imaging studies and psychological tests. Out of 132 subjects, 62 comprised normal and 70 the abnormal finding group. EEG and SPECT were chosen for inspection of functional brain imaging. MMPI and K-WAIS were chosen for psychological test. The subjects were further divided into right hemispheric damage, left hemispheric damage, both hemispheric damage, diffuse damage group and negative group in order to find out whether any differences in the psychological lest results could be localized. The results are as follows : 1) The abnormal finding group, the EEG and SPECT were proven to be a good predictor of brain lesion. This implies that even in the functional brain studies, abnormalities are more easily detected if there are visible brain lesions. 2) The FSIQ of the abnormal finding group is lower than that of normal finding group. this difference is mainly due to low V1Q. The left hemispheric damage group lend to shaw low V1Q. This lowered in was the difference between left hemispheric damage group and negative group. Furthermore, there were no group differences in the PIQ. It is concluded that K-WAIS is effective as evaluator of VIQ mainly of those patients with left hemispheric damage and it is ineffective as a evaluator of PIQ. 3) In the MMPI profile, the both groups displayed high neurotic profiles. There was no difference in the psychotic profiles. The scores of the Depression and Hystery were high in abnormal finding group. This can be seen as one of the lypical findings of chronic head trauma patients. 4) The abnormal finding group tend to be diagnosed as organic mental disorder in the psychological tests more frequently.

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FORMATION OF PROTO-GLOBULAR CLUSTER CLOUDS BY THERMAL INSTABILITY

  • KANG HYESUNG;LAKE GEORGE;RYU DONGSU
    • 천문학회지
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    • 제33권2호
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    • pp.111-121
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    • 2000
  • Many models of globular cluster formation assume the presence of cold dense clouds in early universe. Here we re-examine the Fall & Rees (1985) model for formation of proto-globular cluster clouds (PGCCs) via thermal instabilities in a protogalactic halo. We first argue, based on the previous study of two-dimensional numerical simulations of thermally unstable clouds in a stratified halo of galaxy clusters by Real et al. (1991), that under the protogalactic environments only nonlinear (${\delta}{\ge}1$) density inhomogeneities can condense into PGCCs without being disrupted by the buoyancy-driven dynamical instabilities. We then carry out numerical simulations of the collapse of overdense douds in one-dimensional spherical geometry, including self-gravity and radiative cooling down to T = $10^4$ K. Since imprinting of Jeans mass at $10^4$ K is essential to this model, here we focus on the cases where external UV background radiation prevents the formation of $H_2$ molecules and so prevent the cloud from cooling below $10^4$ K. The quantitative results from these simulations can be summarized as follows: 1) Perturbations smaller than $M_{min}\~(10^{5.6}\;M{\bigodot})(nh/0.05cm^{-3})^{-2}$ cool isobarically, where nh is the unperturbed halo density, while perturbations larger than $M_{min}\~(10^8\;M{\bigodot})(nh/0.05cm^{-3})^{-2}$ cool isochorically and thermal instabilities do not operate. On the other hand, intermediate size perturbations ($M_{min} < M_{pgcc} < M_{max}$) are compressed supersonically, accompanied by strong accretion shocks. 2) For supersonically collapsing clouds, the density compression factor after they cool to $T_c = 10^4$ K range $10^{2.5} - 10^6$, while the isobaric compression factor is only $10^{2.5}$. 3) Isobarically collapsed clouds ($M < M_{min}$) are too small to be gravitationally bound. For supersonically collapsing clouds, however, the Jeans mass can be reduced to as small as $10^{5.5}\;M_{\bigodot}(nh/0.05cm^{-3})^{-1/2}$ at the maximum compression owing to the increased density compression. 4) The density profile of simulated PGCCs can be approximated by a constant core with a halo of $p{\infty} r^{-2}$ rather than a singular isothermal sphere.

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정보기술 아키텍처를 위한 기술참조모델을 지원하는 표준프로파일 관리시스템 개발에 관한 연구 (A Study on the Development of Standard Profiles Management System which supports the Technical Reference Model for Information Technology Architecture)

  • 양진혁;김영도;정희준;양진영;유명환
    • 정보처리학회논문지D
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    • 제8D권6호
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    • pp.665-672
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    • 2001
  • 정보기술 아키텍처는 정보시스템에 대한 요구사항을 충족시키고, 상호운용성 및 보안성을 보장하기 위한 일환으로 정립된 개념으로서, 조직에서 사용되는 정보들을 지원하기 위한 정보기술과 그 구성요소들을 분석하고 이들간의 관계를 구조적으로 정리한 체계로서 정의된다. 정보기술 아키텍처는 전사적 아키텍처, 기술참조모델, 그리고 표준프로파일로 구성된다. 정보기술 아키텍처의 한 구성요소인 표준프로파일은 정보기술 표준들의 집합이다. 본 논문에서는 정보기술 아키텍처를 구성 및 활용하기 위하여 기술참조모델에 기반을 둔 표준프로파일 관리시스템 구축에 대한 정보기술의 활용에 대해 언급한다. 구현된 표준프로파일 관리시스템은 국내에서 최초로 시도되는 정보기술 아키텍처 분야에 대한 구현으로서, JSP 및 Java와 같은 객체지향 언어를 사용하여 소프트웨어를 설계하였다. 그리고, UML 표기법에 근거한 기본 및 상세 설계서의 작성, 소프트웨어 아키텍처를 구성하는 컴포넌트 및 디자인 패턴을 활용한 시스템 설계로 인하여 소프트웨어의 재사용성을 높였다. 또한, 리눅스의 활용, 국산 데이터 베이스의 사용, 아파치와 탐캣과 같은 공개 소프트웨어의 사용으로 인한 향후 시스템 유지보수비용을 절감할 수 있도록 하였다. 마지막으로 국외 표준정보 제공시스템에서는 찾아볼 수 없는 타기관에서 사용하는 표준정보에 대한 참조시스템이 포함되어있고 표준에 대한 제정 및 개정에 대한 일련의 업무처리를 인터넷으로 지원할 수 있는 모듈과 같은 다양한 부가적인 서비스들이 본 정보시스템에 통합되어있다.

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Methanol Extract of Agaricus blazei Murill Reduces Hepatic Damage Induced by $CCl_4$ and High Fat and Improves Liver Lipid Profile in Rats

  • Jung, Myung-Eun;Kwon, Hyuck-Se;Shin, Se-Gye;Jin, Yong-Xie;Han, Eun-Kyung;Ham, Seung-Shi;Kang, Il-Jun;Chung, Cha-Kwon
    • Nutritional Sciences
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    • 제9권4호
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    • pp.267-272
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    • 2006
  • The effect of methanol extract from Agaricus blazei Murill on the hepatotoxicity was investigated $CCl_4$ is one of the oldest and most widely used toxins for the induction of hepatic damages and fibrosis in experimental animals. In this study, male Sprague-Dawley(SD) rats were randomly divided into 6 groups of the control(C), $CCl_4(T),\;CCl_4$ and high fat group(TL) with matching sub-groups of Agaricus blazei Murill extract-fed groups of CA, TA and TLA. Methanol extracts of Agaricus blazei Murill were fed 50 mg/kg B.W daily via drinking water. A 1.2 mL of $CCl_4/kg$ body weight was administered by oral intubation twice a week for total of six times. The levels of total-cholesterol, TG, LDL and LDL-phospholipids were elevated by $CCl_4$ treatment as compared to the control(C). However, Agaricus blazei Murill methanol extract feeding in the group of TA and TLA significantly(p<0.05) decreased TG by 53.1 % and 17.9% compared to the internal control of T and TL, respectively. Triglyceride of TL was increased by 3.33 times(p<0.05) compared to the control(C) with $CCl_4$ and high fat administration from 3.78 mg/g to 12.60 mg/g liver. The extract(CA) also reduced kidney weight compared to the control(C). With the administration of high fat and $CCl_4$(TLA), the extract reduced the organ weight of both liver and kidney and further, significantly reduced TG, total cholesterol and GTP activity. Hepatoprotective effects of Agaricus blazei Murill on GOT, GPT, AP and LDH activities were enhanced by the extract feeding. Electronmicrograph showed that $CCl_4$ deteriorated the structure of cytoplasmic matrix with its uneven distribution. However, the extract reconstituted the damaged cytoplasm and stimulated mitochondriogenesis. The above results suggest that Agaricus blazei Murill may have a possible protective effect against chemically induced liver damage and further help to reduce the symptoms of fatty liver.

Saos-2 세포에서 Doxorubicin에 의한 세포사멸 유도과정에서의 유전자 발현 변화 (Profile of Gene Expression Changes During Doxorubicin Induced Apoptosis of Saos-2)

  • 임정숙;배민재;백석환;김재룡;김정희;김성용
    • Journal of Yeungnam Medical Science
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    • 제22권2호
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    • pp.221-240
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    • 2005
  • 사람의 악성 골종양 세포주 Saos-2 를 이용하여 doxorubicin에 의해 발현이 증가 또는 감소하는 유전자들의 변화를 cDNA microarray를 이용하여 확인하였다. 그 결과 대조군에 비하여 2배 이상 증가 또는 감소하는 유전자 264개, 3배 이상 증가 또는 감소하는 유전자 35개를 선별할 수 있었다. Doxorubicin 처리 후 시간대 별로 발현변화가 비슷한 유전자들을 k-mean clustering으로 분석하여 5가지의 군으로 분류할 수 있었다. A군은 24시간 까지 계속 발현이 증가하는 67개 유전자, B군은 6시간까지는 변화가 없다가 24시간에는 감소하는 108개 유전자, C군은 6시간에 발현의 감소하고 24시간까지 지속되는 33개 유전자, D군은 6시간에 발현의 감소하였으나 24시간에는 다시 발현이 회복되는 5개 유전자, 그리고 E군은 6시간까지는 발현의 변화가 없다가 24시간에 발현이 증가하는 경향을 보이는 51개 유전자로 구분하였다. cDNA microarry 결과 발현차이가 현저한 22개의 유전자들을 대상으로 RT-PCR을 시행하여 발현정도를 비교하였다. cDNA microarry에서 발현증가를 보이는 13개 유전자 중에서, RT-PCR 결과 11개가 그 발현이 증가하였으며, cDNA microarry의 결과에서 발현감소를 보이는 9개 유전자 중에서 RT-PCR 결과에서 2개 유전자만 감소하였다. 이상의 결과 Saos-2 세포에서 doxorubicin에 의해 세포사멸과 세포성장, 세포신호전달, 세포골격, 세포주기, 운반, 대사 등에 관여하는 많은 유전자들의 발현이 변함을 확인할 수 있었다.

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Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE2 pathway

  • Park, Seol-Gi;An, Ju-Hyun;Li, Qiang;Chae, Hyung-Kyu;Park, Su-Min;Lee, Jeong-Hwa;Ahn, Jin-Ok;Song, Woo-Jin;Youn, Hwa-Young
    • Journal of Veterinary Science
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    • 제22권2호
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    • pp.16.1-16.13
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    • 2021
  • Background: Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells. Objectives: This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ). Methods: To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs. Results: Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factor-beta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E2 (PGE2) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ. Conclusions: IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE2, which induces macrophage polarization and increases regulatory T-cell numbers.