Fas ligand 발현이 조혈모세포 이식 거부반응 억제에 미치는 영향

정성철,오현정,장남학,이광수,김규찬 국립보건연구원 1998 국립보건원보 Vol.35 No.-

FAS-FAS ligand system에 의한 배양 각막상피 세포의 세포고사 메커니즘

김재민 대한시과학회 2006 대한시과학회지 Vol.8 No.1

본 연구는 배양 각막 상피세포에 anti - F AS and anti - F AS ligand antibody를 노출시 킨 후 세포고사 메커니즘을 결정하기 위해 시행하였다. 배양각막 상피세포에 antihuman FAS(N-18) goat polyclonal IgG를 50, 200, 500, 1,000 ng/m~ 또는 anti-human FAS ligand(C• 20) goat polyclonal IgG를 500 ng/m~으로 2 일과 4 일 동안 처 리 하였다. 주어진 기간 동안 배양한 후 배양액에 부유한 세포와 부착된 세포를 원심분리와 트립 신 처리 원섬분리를 이용하여 수확하였다. 각막상피세포에 대한 anti - F AS and antiF AS ligand antibody 의 영향을 알아보기 위해 Hoechst 33342 staining과 TUNEL stammg 방법을 이용하여 세포 세포고사 유도를 확인하였다. 세포막 수용체인 FAS protein의 발현을 알아보기 위해 ìmmunocytochemistry 를 시행하였다. anti-FAS antìbody를 처리한 군에서는 대조군에 비해 시간과 농도에 비례하여 후기 세포고사 소 견이 증가하였다. 그러나 anti - F AS ligand antibody를 처리한 군에서는 대조군과 차이 가 거의 없었다. 본 연구의 결과 FAS-FAS ligand system 이 각막상피세포에 발현되었 으며 이는 정상 각막 상피 생리 즉, 세포 탈피에 중요한 기능을 갖는 것으로 사료된다 The purpose of this study was to determine mechanisms of corneal epithelial cell apoptosis in vitro following exposure to anti-FAS and anti-FAS ligand antibody. A cultured human corneal epithelial(HCE) cell line was treated with antihuman FAS(N-18) goat polyclonal IgG(50, 200, 500 and 1,000 ng/rnR,) or anti-human FAS ligand(C-20) goat polyclonal IgG(500 ng/rnR,) for 2 and 4 days. Following incubation both floating and attached cells were harvested by centrifugation and trypsinization/centrifugation respectively. The effect of anti-FAS and anti-FAS ligand antibody on HCE cells was studied using Hoechst 33342 staining. The expression of F AS protein was measured by immunocytochemistry. When compared to controls, anti-FAS antibody induced a time concentration dependent increase in signs of late apoptosis. Anti-FAS ligand antibody did not cause significant apoptosis above background in HCE cells. The FAS-FAS ligand system is expressed in the comeal epithelium and could have important functions in normal comeal physiology.

급성 골수성 백혈병에서 Fas 및 Bcl-2 항원의 발현과 그 임상적 의의

이석,민유홍,정소영,김성철,유내춘,이정윤,권오현,한지숙,고윤웅 大韓血液學會 1996 大韓血液學會誌 Vol.31 No.3

사람 성상세포종 세포주에서 사이토카인에 의한 Fas 및 FasL mRNA의 발현 조절

김옥준,임정희,최철희,최인홍,이병인,최일생 대한신경과학회 1999 대한신경과학회지 Vol.17 No.1

Immunohistochemical analysis of Fas and FLIP in prostate cancers

KIM, SU YOUNG,SONG, SANG YONG,KIM, MIN SUNG,LEE, JI YOUL,LEE, HYUN MOO,CHOI, HAN YONG,YOO, NAM JIN,LEE, SUG HYUNG Blackwell Publishing Ltd 2009 APMIS Vol.117 No.1

<P>Fas-mediated apoptosis is considered a principal pathway for apoptosis induction in normal and cancer cells. Expression of Fas has been reported in prostate tissues several times, but the data were not consistent. Expression of FLICE-like inhibitory protein (FLIP), an inhibitor of Fas-mediated apoptosis, has not been studied by immunohistochemistry in prostate tissues. The aim of this study is to explore whether alterations of Fas and FLIP expression occur in prostate cancer tissues. We analyzed the expression of Fas and FLIP in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray approach. Normal glandular cells of the prostates strongly expressed both Fas and FLIP proteins. Prostate intraepithelial neoplasm also showed a strong Fas immunoreacitity. Fas expression was strongly positive in 60 cancers (56.1%), but the remaining 47 cancers showed no (6.5%) or markedly decreased (37.4%) Fas immunostaining compared with the normal glandular cells of the same patients. By contrast, FLIP expression was strong in most (103/107; 96.3%) of the cancers, and only four cancers (3.7%) showed decreased immunoreactivities compared with the normal cells. The decreased expression of Fas was not associated with pathologic characteristics, including FLIP expression, size of the cancers, age, Gleason score and stage. The decreased expression of Fas in a large fraction of prostate cancers compared with their normal cells suggested that loss of Fas expression might play a role in tumorigenesis in some prostate cancers possibly by inhibiting apoptosis mediated by Fas.</P>

Induction of Fas-Mediated Apoptosis by Interferon-g is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary

Lee, Hye-Jeong,Kim, Ji Young,Park, Ji Eun,Yoon, Yong-Dal,Tsang, Benjamin K.,Kim, Jong-Min The Korean Society of Developmental Biology 2016 발생과 생식 Vol.20 No.4

Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-${\gamma}$) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-${\gamma}$ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-${\gamma}$ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-${\gamma}$ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-${\gamma}$ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (${\geq}1,000U/mL$) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-${\gamma}$ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-${\gamma}$ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent apoptotic response in undifferentiated (or poorly differentiated) granulosa cells at an early (penultimate) stage of follicular development.

위암의 진행에 따른 Fas관련 아포프토시스 유도의 상관성

임성철,황철기,오서진 조선대학교 부설 의학연구소 2000 The Medical Journal of Chosun University Vol.25 No.1

Background and Objectives : The purpose of this study is to determine whether human gastric adenocarcinomas express Fas-L, sFas-L or Fas , whether serum sFas-L leyel is changed in gastric cancer patients after gastrectomy, whether Fas-L expression is associated with increased apoptotic induction, especially, tumor-infiltrating Iymphocytes(TIL) and whether apoptotic induction is associated with the tumor stage and histologic type. Materials and Methods : The author analysed 38 cases of early gastric carcinoma(EGC) and 61 cases of advanced gastric carcinoma (AGC) which received gastric resection from 1997 to 1998. Of them, the number of diffuse type is 38 cases and the number of intestinal type is 61 cases. The author used immunohistochemical staining for Fas, Fas L and CD45, TACS^TM in situ apoptosis detection kit, and sFas ligand ELISA kit. Results : Fas-L was localized to neoplastic cells in 23 cases (23/38; 61%) of EGC group and 40cases (40/61; 66%) of AGC group. The extent of Fas-L expression was variable, with both Fas-L was localized to neoplastic cells in 23 cases (23/38; 61%) of EGC group and 40 cases(40/61; 66%) of group. The extent of Fas-L expression was variable, with both FasL-positive and negative neoplastic region cccuring within. TIL were detected by co-expression of CD4S and TACS on serial histologic sections. TIL adjacent to Fas-L erxressing tumor regions were decreased in number and TIL adjacent to FasL-negative tumor regions were increased in number; apoptotic induction of TIL showed the opposite pattern (p<05). Fas expression was found essentially homogeneously throughout the tumor mass independent of tumor stage. Fas expression showed 39 cases (39/61; 64%) of intestinal type and 26 cases (26/38; 68%) of diffuse type. Labeling indces for tumoral apoptosis in EGC and AGC were 6.72% and 7.13%, respectively and this difference was statistically insignificant. Co-expression of Fas-L and Fas, which occurred over large areas of the tumors, did not result in an enhanced rate of tumor cell apoptosis. The mean serum sFas-L level was significantly higher in patients before treatment compared with controls, whereas in post-gastrectomy patients, it was significantly lower, In addition, tumor stage and other prognostic factors were not associated with Fas and Fas-L expression, serum sFas-L level, number of TIL and apoptotic induction. Conclusion: 'The author demonstrates a statistically significant reduction of TIL concomitant with significantly increased TIL apoptosis adjacent to FasL-expressing regions of gastric adenocarcinomas. Also an elevated level of ·serum sFas-L in the gastric adenocarcinoma group was noted. These findings suggest Fas-mediated apoptotic depletion of TIL in response to Fas-L expression by stomach cancers, and provide the evidence to support the Fas counter-attack as a mechanism of immune escape in gastric cancer. And These findings indicate that the serum sFas-L level is a useful indicator in evaluating postoperative follow-up. In addition, gastric carcinoma cells of the intestinal and diffuse type did not differ in their expression of the Fas-apoptotic system.

Induction of Fas-Mediated Apoptosis by Interferon-g is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary

이혜정,김지영,박지은,윤용달,Benjamin K. Tsang,김종민 한국발생생물학회 2016 발생과 생식 Vol.20 No.4

Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-g) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-g in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-g immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-g was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-g (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (≥ 1,000 U/mL) were required to up-regulate of Fas in differentiated cells isolated from eCGprimed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-g (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-g is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent apoptotic response in undifferentiated (or poorly differentiated) granulosa cells at an early (penultimate) stage of follicular development.

Apoptosis and Expression of Fas nnd Fas Lignnd Genes in Mouse Ovary

윤정미,윤현숙,양현원,김세광,조동제,윤용달 한국발생생물학회 2003 발생과 생식 Vol.7 No.1

Fas는 세포자연사를 유도하는 세포 표면 수용체 단백질로서 면역계에서 중요한 역할을 한다. 이러한 Fas mRNA는 림프조직뿐만 아니 라 비 림프조직에서도 발현한다. 한편 대다수의 난포들은 세포자연사와 연관된 기 작을 통해 난포폐쇄로 진행되는 것으로 알려지고 있으나, 난포폐쇄에 관한 기작은 아직 규명되지 않았다. 따라서 본 연구의 목적은 먼저 생쥐의 난소의 과립세포와 난자에서 Fas와 Fas ligand의 발현 여부를 알아보고, Fas와 Fas liga The Fas antigen (Fas) as a cell-surface receptor protein which mediates apoptosis-inducing signals plays an important role in the immune system. Expression of Fas mRNA is detected not only in lymphoid organs but also in the nonlymphoid organs. In the ovary, most of the follicles is known to undergo atreisa through apoptosis. However, the exact mechanism of atresia was not elucidated yet. Therefore, the purposes of the present study were to investigate the expression of Fas and Fas ligand in mouse ovary and to clarify the relationship between expression of Fas and Fas ligand and atresia of follicle. The result of RT-PCR demonstrated that Fas and Fas ligand mRNA was expressed in ovary, especially granulosa cells and oocytes. The immunohistochemistry showed that the granulosa cells and oocytes in growing follicles were stained for Fas and Fas ligand, but primordial follicles were not. Furthermore, Fas and Fas ligand were intensively stained in the atretic follicles As results of TUNEL staining to detect apoptotic cells in the ovaries, the number of TUNEL-positive (apoptotic) granulosa cells and oocytes increased in the atretic follicles compared to the healthy normal follicles. These results demonstrate that there is the positive relationship between expression of Fas and Fas ligand in granulosa cells and oocyies and apoptosis of them leading to atresia of follicles. It suggests that expression of Fas and Fas ligand could be associated with atresia of follicles in mouse ovary.

Induction of Fas-Mediated Apoptosis by Interferon-γ is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary

Hye-Jeong Lee,Ji Young Kim,Ji Eun Park,Yong-Dal Yoon,Benjamin K. Tsang,Jong-Min Kim 한국발생생물학회 2016 발생과 생식 Vol.20 No.4

Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-γ) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-γ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-γ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-γ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-γ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (≥ 1,000 U/mL) were required to up-regulate of Fas in differentiated cells isolated from eCGprimed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-γ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-γ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent apoptotic response in undifferentiated (or poorly differentiated) granulosa cells at an early (penultimate) stage of follicular development.