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Indoleamine 2,3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines 被引量:12
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作者 Shih Ling HWANG Nancy Pei-Yee CHUNG +1 位作者 Jacqueline Kwai-Yi CHAN Chen-Lung Steve LIN 《Cell Research》 SCIE CAS CSCD 2005年第3期167-175,共9页
Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fet... Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors. 展开更多
关键词 indoleamine 2 3-dioxygenase (ido) dendritic cells ACTIVATION T cell TRYPTOPHAN chemokine.
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Expression of indoleamine 2,3-dioxygenase in a murine model of Aspergillus fumigatus keratitis 被引量:5
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作者 Nan Jiang Gui-Qiu Zhao +7 位作者 Jing Lin Li-Ting Hu Cheng-Ye Che Cui Li Qian Wang Qiang Xu Jie Zhang Xu-Dong Peng 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2016年第4期491-496,共6页
AIM: To observe the presence and expression of indoleamine 2,3-dioxygenase(IDO) during the corneal immunity to Aspergillus fumigatus(A. fumigatus) in the murine models.·METHODS: The murine model of fungal k... AIM: To observe the presence and expression of indoleamine 2,3-dioxygenase(IDO) during the corneal immunity to Aspergillus fumigatus(A. fumigatus) in the murine models.·METHODS: The murine model of fungal keratitis was established by smearing with colonies of A. fumigatus after scraping central epithelium of cornea and covering with contact lenses in C57BL/6 mice. The mice were randomly divided into control group, sham group and A.fumigatus keratitis group. The cornea was monitored daily using a slit lamp and recorded disease score after infection. Corneal lesion was detected by immunofluorescence staining. IDO m RNA and protein were also detected by quantitative reverse transcription-polymerase chain reaction(q RT-PCR) and Western blot.· RESULTS: The disease score and slit lamp photography indicated that disease severity was consistent with corneal inflammation in the murine models, and the disease scores in A. fumigatus keratitis group were obviously higher than those in the sham group. By immunofluorescence staining, IDO was mainly localized in corneal epithelium and stroma in the murine corneal tissues with A. fumigatus keratitis. Compared with the sham group, IDO m RNA expression was significantly enhanced in corneal epithelium infected by A. fumigatus. Furthermore, IDO protein expression detected by Western blot was in accord with transcript levels of IDO m RNA measured by q RT-PCR. IDO protein expression was enhanced after A. fumigatus infection compared with the sham group.·CONCLUSION: IDO is detected in corneal epithelium and stroma locally, which indicates IDO takes part in the pathogenesis of A. fumigatus keratitis and plays a key role in immune regulation at the early stage. 展开更多
关键词 indoleamine 2 3-dioxygenase corneal epithelium fungal keratitis Aspergillus fumigatus innate immune response
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Indoleamine 2,3-dioxygenase adjusts neutrophils recruitment and chemotaxis in Aspergillus fumigatus keratitis 被引量:1
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作者 Shu-Xuan Guo Nan Jiang +2 位作者 Li Zhang Wei Jiang Jing-Jing Ma 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2022年第3期380-387,共8页
AIM: To explore the effect of indoleamine 2,3-dioxygenase(IDO) on recruitment and chemotaxis function of neutrophils in Aspergillus fumigatus(A.fumigatus) keratitis.METHODS: C57BL/6 mice models of A.fumigatus keratiti... AIM: To explore the effect of indoleamine 2,3-dioxygenase(IDO) on recruitment and chemotaxis function of neutrophils in Aspergillus fumigatus(A.fumigatus) keratitis.METHODS: C57BL/6 mice models of A.fumigatus keratitis were established by inoculating hyphae of A.fumigatus evenly on the corneas.The clinical scores and inflammatory cytokines expression were measured respectively on the 1^(st), 3^(th), 5^(th) day after infection.The 1-MT(1 mg/m L) was administered by gavage to exert an inhibitory effect on IDO during infection.The mice were divided into control group, 1-MT group, A.fumigatus(A.F.) group, and 1-MT+A.F.groups.The corneas were monitored by slit lamp microscopy, and recorded disease scores in 3 d after infection.Myeloperoxidase(MPO) assay was done to evaluate the neutrophils infiltration.Immunofluorescence staining was used to detect the recruitment of neutrophils in murine corneas.The m RNA of inflammatory cytokines was measured with reverse transcription-polymerase chain reaction(RT-PCR).RESULTS: The corneal inflammation and the clinical score reached the peak on the 3;day after the corneal infection.The m RNA of inflammatory cytokines of the A.F.group reached the highest on the 3;day after the infection accordingly.Meanwhile, the results of slit light photography indicated that inhibitors of IDO made inflammation more serious contrasted with the A.F.group on the 3;day.Besides, imunofluorescence staining and MPO indicated that 1-MT enhanced the recruitment, infiltration and chemotaxis of neutrophils obviously in contrast to the A.F.group.RT-PCR indicated that 1-MT increased the expression of CXCL-1, ICAM-1, IL-1β, and IL-8 significantly.CONCLUSION: IDO participates in the pathogenesis of A.fumigatus keratitis and plays an important role in inducing immune protection by inhibiting neutrophils-related inflammatory reaction and suppressing recruitment and chemotaxis of the neutrophils. 展开更多
关键词 indoleamine 2 3-dioxygenase KERATITIS NEUTROPHILS Aspergillus fumigatus innate immune
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Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients 被引量:3
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作者 Qiang-hua Zhou Hui Han +13 位作者 Jia-bin Lu Ting-yu Liu Kang-bo Huang Chuang-zhong Deng Zai-shang Li Jie-ping Chen Kai Yao Zi-ke Qin Zhuo-wei Liu Yong-hong Li Sheng-jie Guo Yun-lin Ye Fang-jian Zhou Ran-yi Liu 《Cancer Communications》 SCIE 2020年第1期3-15,共13页
Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of... Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical significance.Methods: IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. The survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. The correlativity was assessed by Pearson’s correlation analysis.Results: The expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/Trp radio (KTR;both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 upregulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008and 0.032, respectively). High expression level of IDO1 in cancer cells and serumKTR were associated with short disease-specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926;95% confidence interval [CI],2.458-19.068;P < 0.001) and pathologic grade (HR, 2.194;95% CI, 1.021-4.529;P = 0.038), only serum KTR (HR, 2.780;95% CI, 1.066-7.215;P = 0.036) was anindependent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon-𝛾 (IFN𝛾, P < 0.001) and immunosuppressivemarkers (programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 and 2;all P < 0.05), and the infiltration ofimmune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumorassociated macrophages, and myeloid-derived suppressor cells;all P < 0.001) inPSCC tissues. Furthermore, the expression of IDO1 was induced by IFN𝛾 in a dosedependent manner in PSCC cells.Conclusions: IFN𝛾-induced IDO1 plays a crucial role in immunoediting andimmunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1catabolic activity, can be utilized as an independent prognostic factor for PSCC. 展开更多
关键词 cytotoxic T-lymphocyte-associated protein 4 IMMUNOSUPPRESSION indoleamine 2 3-dioxygenase 1 INTERFERON-GAMMA kynurenine/tryptophan ratio penile cancer programmed cell death protein 1 programmed death-ligand 1 tumor-infiltrating immune cells
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T-cell proliferation is inhibited by the induction of indoleamine 2,3-dioxygenase in spleen-derived dendritic cells in rat 被引量:8
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作者 XU Jun YAO Ning LI Yuan-dong 《Chinese Medical Journal》 SCIE CAS CSCD 2011年第19期3154-3158,共5页
Background Increasing evidence suggests that, by the production of indoleamine 2, 3-dioxygenase (IDO), dendritic cells (DC) may reduce the activity of T lymphocytes and inhibit T lymphocyte proliferation-induced i... Background Increasing evidence suggests that, by the production of indoleamine 2, 3-dioxygenase (IDO), dendritic cells (DC) may reduce the activity of T lymphocytes and inhibit T lymphocyte proliferation-induced immune tolerance.One promising way is inspired by increasing IDO expression in DG cells for immune tolerance after transplantation. The aim of this work was to examine the effect of interferon-y (IFN-γ) on the expression of IDO by DC.Methods Spleen-derived rat DCs were cultured and induced by cytokines, and the expression of OX62 and surface molecules CD80 and CD86 were measured with flow cytometry. After the DCs were induced by IFN-γ at different concentrations (0, 100, 300, 500 U/ml), the expression levels of IDO mRNA were measured with real-time PCR, and the expression levels of IDO protein in DCs were measured with Western blotting. The allogeneic mixed lymphocyte reaction (MLR) was used to test the effects of DCs incubated with different concentrations of IFN-γ on allogeneic T lymphocyte proliferation.Results Under the microscope, the DCs induced by IFN-γ showed a typical dendritic morphology. The expression rate of OX62 was above 80% and the positive expression rates of CD80 and CD86 were both about 80%. The expressions of IDO mRNA and IDO protein increased gradually with the increase of IFN-γ concentration, showing statistical significance in the differences between the groups (P 〈0.05). Compared with the control DC, the DC incubated with IFN-γ had a notable decrease in allostimulatory activity (P 〈0.05). With the increasing IFN-γ concentration, the T lymphocyte proliferation decreased, and the difference between the groups was also statistically significant (P 〈0.05).Conclusions The highly purified spleen derived rat DCs can be successfully acquired through the improved adhesion in-vitro method. IFN-γ can induce increased expression of IDO in spleen-derived rat DCs and reduce the spleen DCs' capacity to stimulate the proliferation of allogeneic T cells. 展开更多
关键词 dendritic cell indoleamine 2 3-dioxygenase y-interferon T lymphocyte
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Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer 被引量:5
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作者 Wen-Juan Ma Xing Wang +4 位作者 Wen-Ting Yan Zhong-Guo Zhou Zhi-Zhong Pan Gong Chen Rong-Xin Zhang 《World Journal of Gastroenterology》 SCIE CAS 2018年第20期2181-2190,共10页
AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) patients.METHODS We retrospectively studied the medical records of... AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) patients.METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) outcomes.RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index(P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC. 展开更多
关键词 PROGNOSIS indoleamine-2 3-dioxygenase 1 CYCLOOXYGENASE 2 Colorectal cancer
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吲哚胺2,3-双加氧酶(IDO)参与抑郁症发病机制的研究进展 被引量:3
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作者 李红 简坤 《宜春学院学报》 2016年第9期24-28,共5页
抑郁症的发病机制复杂,至今尚未完全清楚。迄今为止,关于抑郁症的发病机制有多种假说,分别从不同方面阐述了抑郁症的发病机制,如:下丘脑-垂体-肾上腺皮质(hypothalamus-pituitary-adrenocortical,HPA)功能亢进、促炎性细胞因子以及中枢... 抑郁症的发病机制复杂,至今尚未完全清楚。迄今为止,关于抑郁症的发病机制有多种假说,分别从不同方面阐述了抑郁症的发病机制,如:下丘脑-垂体-肾上腺皮质(hypothalamus-pituitary-adrenocortical,HPA)功能亢进、促炎性细胞因子以及中枢神经元损伤等。但各种机制均提及到抑郁症的致病因子与吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)的调节有关,IDO成为枢纽性因素。IDO可能在抑郁症的发病中具有广阔的研究前景。本文通过查阅国内外最近五年的大量中、英文文献对吲哚胺2,3-双加氧酶(IDO)参与抑郁症发病机制的研究进展作一详细综述。 展开更多
关键词 抑郁症 吲哚胺2 3-双加氧酶(ido) 细胞因子 5-羟色胺
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IDO基因稳定转染HepG_2细胞系的建立 被引量:3
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作者 刘春亮 冯惠枝 +5 位作者 刘燕 卜晓倩 申慧琴 张瑞 唐运萍 王琦 《医学研究杂志》 2012年第2期68-70,共3页
目的建立稳定转染IDO基因的HepG2细胞系,为进一步研究IDO基因在肝癌免疫逃逸中的作用奠定基础。方法应用脂质体将真核细胞表达质粒pcDNA3.1-IDO和空载质粒pcDNA3.1转染入HepG2细胞,经G418进行筛选后,挑取单克隆进行培养,用反转录酶聚合... 目的建立稳定转染IDO基因的HepG2细胞系,为进一步研究IDO基因在肝癌免疫逃逸中的作用奠定基础。方法应用脂质体将真核细胞表达质粒pcDNA3.1-IDO和空载质粒pcDNA3.1转染入HepG2细胞,经G418进行筛选后,挑取单克隆进行培养,用反转录酶聚合酶链反应(RT-PCR)和Western blot方法验证获得的表达细胞株。结果经RT-PCR和Western blotting检测证实空质粒转染组和空白对照组HepG2细胞无IDO基因及蛋白的表达,而重组质粒组的HepG2细胞表达IDO基因和蛋白。结论 pcDNA3.1-IDO质粒体外稳定转染人肝癌细胞HepG2,可以有效地使IDO基因在RNA水平和蛋白水平均表达,成功建立了稳定转染基因IDO的HepG2细胞系,为进一步探讨该基因的功能奠定了一定基础。 展开更多
关键词 吲哚胺2 3-双加氧酶(ido) HEPG2细胞 稳定转染
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Vav1在吲哚胺2,3双加氧酶抑制T细胞中的作用初探 被引量:2
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作者 李润美 魏枫 +3 位作者 于津浦 李慧 任秀宝 郝希山 《中国免疫学杂志》 CAS CSCD 北大核心 2009年第9期786-791,共6页
目的:探讨吲哚胺2,3双加氧酶(IDO)抑制T细胞中信号传导分子Vav1的分子机制。方法:应用稳定表达IDO的CHO细胞株,与纯化的外周血T细胞共孵育,检测IDO抑制T细胞增殖,诱导凋亡的情况,通过semi-quantitative RT-PCR检测T细胞中Vav1、IL-2 mRN... 目的:探讨吲哚胺2,3双加氧酶(IDO)抑制T细胞中信号传导分子Vav1的分子机制。方法:应用稳定表达IDO的CHO细胞株,与纯化的外周血T细胞共孵育,检测IDO抑制T细胞增殖,诱导凋亡的情况,通过semi-quantitative RT-PCR检测T细胞中Vav1、IL-2 mRNA表达变化;Western blot及免疫沉淀技术检测Vav1蛋白表达及活化情况。结果:IDO可抑制T细胞的增殖。T细胞中Vav1和IL-2 mRNA水平明显下降(P<0.05)。而且,IDO还能使Vav1蛋白的表达和磷酸化水平降低。结论:研究证实在肿瘤局部产生于抗原呈递细胞或肿瘤细胞的IDO,可能通过抑制细胞内重要的信号传导蛋白Vav1的表达和磷酸化过程,使肿瘤浸润淋巴细胞的主动免疫受损,有利于肿瘤发生免疫逃逸。 展开更多
关键词 吲哚胺2 3双加氧酶 Vav1 IL-2 磷酸化
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2-苯基-1,3,4-噻二唑衍生物的合成与活性评价
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作者 朱锦锦 徐露玫 +1 位作者 张丹 乔春华 《化学研究与应用》 CAS CSCD 北大核心 2018年第10期1668-1677,共10页
合成18个2-苯基-1,3,4噻二唑系列化合物并评价其对吲哚胺2,3-双加氧酶1(Indoleamine 2,3-Dioxygenase1,IDO1)抑制活性。生物上建立酶活性检测体系,检测2-苯基-1,3,4噻二唑类化合物的IDO1抑制活性。结果表明对18个噻二唑类化合物进行酶... 合成18个2-苯基-1,3,4噻二唑系列化合物并评价其对吲哚胺2,3-双加氧酶1(Indoleamine 2,3-Dioxygenase1,IDO1)抑制活性。生物上建立酶活性检测体系,检测2-苯基-1,3,4噻二唑类化合物的IDO1抑制活性。结果表明对18个噻二唑类化合物进行酶活性检测,分析得到相关的构效关系,其中A16表现出较好的IDO1抑制活性。 展开更多
关键词 2-苯基-1 3 4噻二唑类 吲哚胺2 3-双加氧酶1 ido1抑制剂
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犬尿氨酸途径与2型糖尿病相关性研究进展
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作者 马晓婕 高嘉良 +1 位作者 杨庭 王洪武 《生命的化学》 CAS 2024年第8期1442-1448,共7页
2型糖尿病(type 2 diabetes mellitus,T2DM)是由胰岛素抵抗和(或)胰岛素分泌相对不足引起的,以持续性高血糖为主要特征的一种糖、脂、蛋白质代谢紊乱性的慢性炎症性疾病,占全部糖尿病的90%以上。色氨酸可通过犬尿氨酸途径(kynurenine pa... 2型糖尿病(type 2 diabetes mellitus,T2DM)是由胰岛素抵抗和(或)胰岛素分泌相对不足引起的,以持续性高血糖为主要特征的一种糖、脂、蛋白质代谢紊乱性的慢性炎症性疾病,占全部糖尿病的90%以上。色氨酸可通过犬尿氨酸途径(kynurenine pathway,KP)、血清素(5-羟色胺)途径和肠道微生物(吲哚)途径在机体内进行分解代谢。近年来,大量研究发现,色氨酸代谢特别是KP的代谢异常可能影响T2DM的发生与发展。本文从KP及KP代谢物的生理病理作用、KP的代谢过程、KP代谢产物及参与该途径代谢的关键酶在T2DM中的变化情况、KP在T2DM病理机制中的作用以及通过调控KP来改善或延缓T2DM进展的具体策略等方面进行综述,以调节KP为新的切入点为T2DM提供可能的防治思路。 展开更多
关键词 色氨酸代谢 犬尿氨酸途径 吲哚胺2 3-双加氧酶 2型糖尿病
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Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway 被引量:8
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作者 Yumiao Zhao Jiaxin Sun +13 位作者 Yin Li Xiuman Zhou Wenjie Zhai Yahong Wu Guanyu Chen Shanshan Gou Xinghua Sui Wenshan Zhao Lu Qiu Yongjie Yao Yixuan Sun Chunxia Chen Yuanming Qi Yanfeng Gao 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第9期2835-2849,共15页
Tryptophan 2,3-dioxygnease 2(TDO2) is specific for metabolizing tryptophan to kynurenine(KYN),which plays a critical role in mediating immune escape of cancer.Although accumulating evidence demonstrates that TDO2 over... Tryptophan 2,3-dioxygnease 2(TDO2) is specific for metabolizing tryptophan to kynurenine(KYN),which plays a critical role in mediating immune escape of cancer.Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers,its tumor-promoting role in esophageal squamous cell carcinoma(ESCC) remains unclear.Here,we observed that TDO2 was overexpressed in ESCC tis sues and correlated significantly with lymph node metastasis,advanced clinical stage,and unfavorable prognosis.Functional experiments showed that TDO2 promoted tumor cell proliferation,migration,and colony formation,which could be prevented by inhibition of TDO2 and aryl hydrocarb on receptor(AHR).Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model,tumor burden of C57 BL/6 mice with ESCC induced by 4-NQO,enhance the expression of phosphorylated AKT,with subsequent pho sphorylation of GSK3β,and polarization of M2 macrophages by upregulating interleukin-8(IL-8) to accelerate tumor progression in the tumor microenvironment(TME).Collectively,our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC,and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC. 展开更多
关键词 Tryptophan 2 3-dioxygenase 2 M2 macrophage Esophageal squamous cell carcinoma IL-8 KYN
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Recombinant adenovirus with human indoleamine-2,3- dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells 被引量:5
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作者 CHEN Yong-bing SHI Xian-jie +4 位作者 LU Gang NIE Hong-feng SHEN Xiao-qing YU Cong-hui GONG Jian-ping 《Chinese Medical Journal》 SCIE CAS CSCD 2011年第19期3159-3163,共5页
Background Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we construct... Background Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo experiments.Methods The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus (CMV) promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hlDO gene and HBVpreS gene was packaged and amplified in 293 cells.Integration was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hlDO and HBVpreS was detected by RT-PCR and Western blotting respectively.Results The recombinant adenovirus was produced successfully. Its titer was 2.5x109 efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 cells.Conclusion The transfer of hlDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hlDO and HBVpreS would provide the experimental basis for future studies. 展开更多
关键词 indoleamine-2 3-dioxygenase recombined adenovirus hepatitis B virus HepG2 cell
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新型1,2,3-三氮唑类衍生物的合成及抗炎活性研究
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作者 孙泽人 翟冰新 +6 位作者 何光超 沈慧 陈琳雅 张杉 邹毅 朱启华 徐云根 《有机化学》 SCIE CAS CSCD 北大核心 2023年第6期2143-2155,共13页
吲哚胺2,3-双加氧酶2(IDO2)在炎症特别是类风湿性关节炎(RA)方面的作用逐渐被阐明,IDO2成为RA治疗的潜在靶点.目前尚未见活性强、选择性高的IDO2小分子抑制剂被报道.以吲哚胺2,3-双加氧酶1(IDO1)抑制剂epacadostat为先导化合物,借助计... 吲哚胺2,3-双加氧酶2(IDO2)在炎症特别是类风湿性关节炎(RA)方面的作用逐渐被阐明,IDO2成为RA治疗的潜在靶点.目前尚未见活性强、选择性高的IDO2小分子抑制剂被报道.以吲哚胺2,3-双加氧酶1(IDO1)抑制剂epacadostat为先导化合物,借助计算机辅助药物设计,设计合成了24个未见文献报道的1,2,3-三氮唑类衍生物.生物活性研究表明,目标化合物均具有IDO1和IDO2酶抑制活性,其中(Z)-N-((1-(2-((4-(N-(3-溴-4-氟苯基)-N’-羟基甲脒)-1,2,5-噁二唑-3-基)氨基)乙基)-1H-1,2,3-三氮唑-4-基)甲基)呋喃-2-甲酰胺(I-11)在100nmol/L浓度下对IDO1和IDO2酶的抑制率分别为76%和49%,优于先导化合物epacadostat(分别为62%和25%).抗炎活性研究表明,化合物I-11可有效抑制脂多糖(LPS)诱导的RAW264.7细胞炎症因子TNF-α的分泌,并且对小鼠耳肿胀抑制率(56.81%,100 mg/kg,灌胃)优于阳性对照Naproxen(45.29%,150 mg/kg,灌胃),表现出较好的抗炎活性. 展开更多
关键词 吲哚胺2 3-双加氧酶1(ido1) 吲哚胺2 3-双加氧酶2(ido2) 1 2 3-三氮唑 抗炎活性
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Trp-IDO1,2/TDO2-Kyn代谢通路介导类风湿关节炎的研究进展 被引量:7
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作者 常艳 魏伟 《药学学报》 CAS CSCD 北大核心 2019年第9期1547-1553,共7页
类风湿关节炎(rheumatoid arthritis, RA)是以自身反应性T细胞和B细胞过度活化,自身抗体大量产生为特征,多关节受累为主要表现的自身免疫病。在遗传和环境等因素影响下,固有免疫和适应性免疫功能紊乱是其发病的根本原因。近年来,'... 类风湿关节炎(rheumatoid arthritis, RA)是以自身反应性T细胞和B细胞过度活化,自身抗体大量产生为特征,多关节受累为主要表现的自身免疫病。在遗传和环境等因素影响下,固有免疫和适应性免疫功能紊乱是其发病的根本原因。近年来,'免疫代谢学'快速发展,在不同能量代谢途径及相关分子调控免疫细胞分化与功能等方面取得重要进展。多项研究表明, Trp-IDO1,2/TDO2-Kyn代谢通路介导了RA等自身免疫病的病理机制和发生发展。本文综述了此代谢通路中色氨酸(tryptophan, Trp)和犬尿氨酸(kynurenine, Kyn)等代谢物以及限速酶吲哚胺-2,3-双加氧酶1 (indoleamine 2,3-dioxygenase 1, IDO1)、吲哚胺-2,3-双加氧酶2 (indoleamine 2, 3-dioxygenase 2, IDO2)和色氨酸-2,3-双加氧酶2 (tryptophan-2,3-dioxygenase 2, TDO2)介导RA炎症免疫反应和滑膜炎症的作用和研究进展,为阐明RA新的病理机制和发现新的药物靶点提供重要依据。 展开更多
关键词 类风湿关节炎 免疫代谢 色氨酸 犬尿氨酸 吲哚胺-2 3-双加氧酶1 吲哚胺-2 3-双加氧酶2 色氨酸-2 3-双加氧酶2
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脂质体介导pIDO-EGFP转染原代培养软骨细胞的初步研究 被引量:3
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作者 段小红 何贤辉 +5 位作者 崔鹏程 王晓燕 吴明明 史剑波 许庚 江逊 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2007年第12期1110-1112,1116,共4页
目的:检测脂质体介导pIDO-EGFP转染原代培养的C57小鼠关节软骨细胞的瞬时表达及转染效率,建立原代培养的小鼠关节软骨细胞转染方法。方法:大肠杆菌中扩增pIDO-EGFP质粒,在最优化条件下通过lipofectamine2000TM转染试剂将pIDO-EGFP质粒... 目的:检测脂质体介导pIDO-EGFP转染原代培养的C57小鼠关节软骨细胞的瞬时表达及转染效率,建立原代培养的小鼠关节软骨细胞转染方法。方法:大肠杆菌中扩增pIDO-EGFP质粒,在最优化条件下通过lipofectamine2000TM转染试剂将pIDO-EGFP质粒转入原代培养的小鼠关节软骨细胞,应用荧光显微镜和激光共聚焦显微镜观察其转染过程及瞬时表达情况,流式细胞术检测其转染效率。结果:质粒携带的增强型绿色荧光蛋白在转染后24h得到了明显表达,48h后流式细胞术检测其转染效率为36.43%,未影响软骨细胞贴壁过程。结论:经绿色荧光蛋白检测表明,脂质体成功地将IDO基因转染进入原代培养的软骨细胞。转染后的软骨细胞在体外仍能存活,在最优化的条件下能达到良好的瞬时转染效率,为组织工程化软骨细胞基因导入和基因修饰提供了思路。 展开更多
关键词 基因转染 软骨细胞 基因表达 吲哚胺2 3-双加氧酶 绿色荧光蛋白
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吲哚胺2,3二氧化酶在造血干细胞移植的研究进展
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作者 叶启翔 方建培 《中华妇幼临床医学杂志(电子版)》 CAS 2011年第4期296-299,共4页
吲哚胺2,3二氧化酶(indoleamine2,3-dioxygenase,IDO)通过诱导色氨酸分解,调节树突状细胞(dendritic cells,DCs)及T细胞等途径实现造血干细胞移植(hematopoietic stemcell transplantation,HSCT)后诱导T细胞免疫耐受,防止移植物抗宿主病... 吲哚胺2,3二氧化酶(indoleamine2,3-dioxygenase,IDO)通过诱导色氨酸分解,调节树突状细胞(dendritic cells,DCs)及T细胞等途径实现造血干细胞移植(hematopoietic stemcell transplantation,HSCT)后诱导T细胞免疫耐受,防止移植物抗宿主病(graft versus host disease,GVHD)的发生及提高移植物存活率。调控吲哚胺2,3二氧化酶已成为提高造血干细胞移植成功率的治疗靶点。 展开更多
关键词 吲哚胺2 3二氧化酶 造血干细胞移植 免疫耐受 移植物抗宿主病
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哈萨克族食管癌患者外周血IDO检测的临床意义
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作者 常英英 黄艳春 《新疆医科大学学报》 CAS 2011年第1期74-76,共3页
目的探讨哈萨克族食管癌患者外周血中吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygenase,IDO)的表达水平及其与食管癌临床病理特征的关系。方法用RT-PCR法检测50例哈萨克族食管癌患者治疗前外周血、20例正常人外周血中IDOmRNA的表达情况... 目的探讨哈萨克族食管癌患者外周血中吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygenase,IDO)的表达水平及其与食管癌临床病理特征的关系。方法用RT-PCR法检测50例哈萨克族食管癌患者治疗前外周血、20例正常人外周血中IDOmRNA的表达情况。结果 IDOmRNA在食管癌患者外周血中的表达为(1.836±0.583)×103,显著高于正常人的(0.145±0.024)×103(P<0.05);食管癌外周血中IDOmRNA的表达与肿瘤的临床分期和淋巴结转移有关(P<0.05);年龄、性别以及肿瘤的生长部位与IDOmRNA的表达无关(P>0.05)。结论 IDOmRNA在新疆哈萨克族食管癌患者外周血中存在高表达,其表达程度与食管癌的发生,发展和转移有着密切的关系。 展开更多
关键词 吲哚胺2 3双加氧酶 哈萨克族 食管癌 逆转录-聚合酶链式反应
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包虫囊液体外诱导小鼠脾脏淋巴细胞TLR2和IDO表达的实验研究
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作者 冯凯 高飞 +4 位作者 马钰涛 郁邦兴 李亮 郭保平 单骄宇 《中国病原生物学杂志》 CSCD 北大核心 2020年第6期649-654,660,共7页
目的研究细粒棘球蚴囊液对体外培养小鼠脾脏淋巴细胞TLR2和IDO表达的影响。方法制备小鼠脾脏淋巴细胞悬液,接种于24孔培养板中进行培养,用不同浓度比的包虫囊液(1∶10、1∶100)进行干预。分别在干预后12、24、36 h收集2份细胞及1份细胞... 目的研究细粒棘球蚴囊液对体外培养小鼠脾脏淋巴细胞TLR2和IDO表达的影响。方法制备小鼠脾脏淋巴细胞悬液,接种于24孔培养板中进行培养,用不同浓度比的包虫囊液(1∶10、1∶100)进行干预。分别在干预后12、24、36 h收集2份细胞及1份细胞培养上清,一份细胞用于Trizol法提取总RNA,通过实时荧光定量PCR检测TLR2、IDO、IL-5的mRNA相对表达水平,另一份细胞采用Western blot方法检测TLR2、IDO蛋白。细胞上清中的IL-6、TGF-β含量采用ELISA法检测。对小鼠脾脏淋巴细胞中IDO与TLR2 mRNA的表达进行线性相关分析。结果实时荧光定量PCR检测HCF为1∶10、1∶100时均可上调小鼠脾脏淋巴细胞TLR2、IDO、IL-5 mRNA的表达,其中1∶100稀释的HCF在24h时分别为0.282±0.144、0.218±0.036、0.648±0.148,与对照组0.006±0.003、0.002±0.000、0.008±0.001比较差异均有统计学意义(P<0.05);Western blot检测TLR2和IDO的表达均可被HCF上调,且在低浓度HCF(1∶100)上调更为显著;ELISA检测HCF干预24 h后细胞上清中的IL-6、TGF-β含量升高,其中在HCF1∶100时,相应含量分别为(296.495±12.495)pg/ml和(449.700±5.350)pg/ml,与对照组(67.328±5.839)pg/ml和(324.200±8.065)pg/ml比较差异均有统计学意义(P<0.05)。线性相关分析显示,小鼠脾脏淋巴细胞IDO与TLR2 mRNA表达水平呈正相关(R^2=0.9887,P<0.01)。结论包虫囊液对小鼠脾脏淋巴细胞TLR2和IDO的表达具有上调作用,故认为在CE慢性感染过程中TLR2和IDO共同发生负性免疫调控作用以促进Th2型反应,导致包虫感染过程中的免疫逃避。 展开更多
关键词 包虫囊液 脾脏淋巴细胞 TOLL样受体2 吲哚胺2 3-双加氧酶 免疫逃避
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吲哚胺加双氧酶的表达调控THP-1巨噬细胞的极化 被引量:6
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作者 王险峰 王昊 +2 位作者 张帆 刘浩 杜军 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2014年第9期901-905,共5页
目的研究吲哚胺加双氧酶(IDO)对巨噬细胞表型转化的影响。方法以10 ng/mL佛波酯诱导THP-1人单核细胞,建立分化的巨噬细胞模型,分别以100 U/mL IFN-γ和100 ng/mL巨噬细胞集落刺激因子(M-CSF)刺激分化的THP-1细胞,获得M1型和M2型巨噬细胞... 目的研究吲哚胺加双氧酶(IDO)对巨噬细胞表型转化的影响。方法以10 ng/mL佛波酯诱导THP-1人单核细胞,建立分化的巨噬细胞模型,分别以100 U/mL IFN-γ和100 ng/mL巨噬细胞集落刺激因子(M-CSF)刺激分化的THP-1细胞,获得M1型和M2型巨噬细胞,利用实时定量PCR(qRT-PCR)、流式细胞术和Western blot法检测巨噬细胞HLA-DR、CC型趋化因子受体7(CCR7)、IL-12p35、IL-10、CXCR4和IDO的表达变化。采用细胞转染实验对分化的THP-1细胞进行IDO的过表达和针对IDO基因的siRNA干扰实验,检测其IL-12p35、CCR7、IL-10和CXCR4的表达变化。结果 IFN-γ可诱导THP-1细胞向M1型发生转化并上调IDO的表达。而在巨噬细胞内过表达IDO促进THP-1向M2型极化,沉默细胞内的IDO基因则导致THP-1细胞极化为M1型。结论 IDO表达可调控巨噬细胞极化。 展开更多
关键词 吲哚胺加双氧酶 巨噬细胞表型转化 IFN-Γ 免疫耐受
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