Indoleamine 2,3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines

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.

Expression of indoleamine 2,3-dioxygenase in a murine model of Aspergillus fumigatus keratitis

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.

Indoleamine 2,3-dioxygenase adjusts neutrophils recruitment and chemotaxis in Aspergillus fumigatus keratitis

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.

Forkhead box P3 and indoleamine 2,3-dioxygenase co-expression in Pakistani triple negative breast cancer patients

BACKGROUND Forkhead box P3(FOXP3)is a specific marker for immunosuppressive regulatory T(T-reg)cells.T-regs and an immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO),are associated with advanced disease in cancer.AIM To evaluate the co-expression of FOXP3 and IDO in triple negative breast cancer(TNBC)with respect to hormone-positive breast cancer patients from Pakistan.METHODS Immunohistochemistry was performed to analyze the expression of FOXP3,IDO,estrogen receptor,progesterone receptor,and human epidermal growth factor receptor on tissues of breast cancer patients(n=100):Hormone-positive breast cancer(n=51)and TNBC(n=49).A total of 100 patients were characterized as FOXP3 negative vs positive and further categorized based on low,medium,and high IDO expression score.Univariate and multivariate logistic regression models were used.RESULTS Out of 100 breast tumors,25%expressed FOXP3 positive T-regs.A significant coexpression of FOXP3 and IDO was observed among patients with TNBC(P=0.01)compared to those with hormone-positive breast cancer.Two variables were identified as significant independent risk factors for FOXP3 positive:IDO expression high(adjusted odds ratio(AOR)5.90;95%confidence interval(CI):1.22-28.64;P=0.03)and TNBC(AOR 2.80;95%CI:0.96-7.95;P=0.05).CONCLUSION Our data showed that FOXP3 positive cells might be associated with high expression of IDO in TNBC patients.FOXP3 and IDO co-expression may also suggest its involvement in disease,and evaluation of FOXP3 and IDO expression in TNBC patients may offer a new therapeutic option.

26S proteasome inhibitors inhibit dexamethasone-dependent increase of tyrosine aminotransferase and tryptophan 2,3-dioxygenase mRNA levels in primary cultured rat hepatocytes

Dexamethasone (Dex), a ligand for transcriptional enhancement of tyrosine aminotransferase (TAT) and tryptophan 2,3-dioxygenase (TO) genes, (100 nM) maximally increased these mRNA levels at 12 h and 7 h in primary cultured rat hepatocytes and the nuclear fraction, respectively. Lactacystin (5 μM) and epoxomicin (0.5 μM), 26S proteasome inhibitors, significantly suppressed the Dex-dependent maximum increase of TAT and TO mRNA levels in the cells and the nuclear fraction. Electrophoretic mobility shift assay demonstrated that lactacystin did not affect binding of glucocorticoid receptor to glucocorticoid responsive element. Furthermore, lactacystin did not affect the activation of GRE luciferase reporter by Dex transfected to the cells. The results demonstrate that 26S proteasome is positively involved in the Dex-dependent increase of TAT and TO mRNA levels in the cells and suggest that the mechanism of action of 26S proteasome may be degradation of some RNase(s), which breaks down TAT and TO mRNAs.

左归丸含药血清对ανβ3、HLA-G、HOXA10、Fas/FasL、IDO在人早孕绒毛膜组织中表达的影响

目的探讨左归丸对体外人早孕绒毛膜组织ανβ3、HLA-G、HOXA10、Fas/Fas L和IDO基因表达的影响。方法对体外培养的人早孕绒毛膜组织加入2%、5%或10%的鼠左归丸含药血清培养24-72 h。同时,在组织培养中加入孕酮作为阳性对照而仅有基础培养基为空白对照。采用Q-PCR技术检测ανβ3、HLA-G、HOXA10、Fas/Fas L和IDO mRNA的表达。采用特异ELISA试剂盒检测定量分析ανβ3和HLA-G的蛋白表达。结果 5%含药血清处理的绒毛膜组织的ανβ3、HLA-G、HOXA10、Fas/Fas L、IDO基因表达均显著高于阳性对照组及空白组(P<0.05)。5%含药血清处理的绒毛膜组织的ανβ3蛋白标点及2%含药血清处理的绒毛膜组织的HLA-G蛋白表达明显高于阳性对照组及空白组(P<0.05)。结论左归丸可能具有增加ανβ3、HLA-G、HOXA10、Fas/Fas L和IDO基因表达的作用,可能是该中药复方治疗不孕症分子生物学机理之一。

Foxp3,IDO在小鼠角膜移植免疫排斥反应的表达

背景:移植免疫反应是导致角膜移植术后失败的主要原因,但其具体发病机制不明确。有研究报道,Foxp3和吲哚胺2,3-二氧化酶(indoleamine 2,3-dioxygenase,IDO)与移植免疫有关。目的:研究Foxp3,IDO在小鼠角膜移植免疫排斥反应中的作用。方法:以C57BL/6小鼠为供体,BALB/c小鼠为受体建立角膜移植实验模型。将30只BALB/c小鼠随机分为3组,正常组6只;角膜移植组12只;地塞米松治疗组12只。角膜移植组:给予生理盐水;地塞米松治疗组:给予地塞米松注射液10 mg/kg,分别于角膜移植术后0,2,4,6,8,10 d经腹腔注射给药。用裂隙灯观察移植排斥情况,免疫组织化学检测植片γ-干扰素表达,Real-time PCR检测植片内Foxp3 mRNA,IDO mRNA的表达。结果与结论:(1)地塞米松治疗组发生排斥反应时间(20.667±1.033)d,较角膜移植组(14.833±1.472)d明显延迟(P<0.05);(2)角膜移植组术后第14天角膜植片内γ-干扰素及Foxp3 mRNA,IDO mRNA的表达较地塞米松治疗组明显增强(P<0.05);(3)结果提示,γ-干扰素及Foxp3,IDO在角膜移植免疫排斥反应过程中发挥重要的作用,降低角膜植片γ-干扰素及Foxp3,IDO表达可能有助于诱导耐受。

吲哚-2，3双加氧酶（IDO）调节免疫的最新进展

吲哚胺2,3-双加氧酶（IDO）是一种含血红素限速酶，其催化色氨酸转化为犬尿氨酸，而犬尿氨酸是色氨酸主要代谢产物。IDO已经在非肝细胞中被发现，主要表达于滋养层细胞，树突细胞，单核细胞和巨噬细胞。IDO的表达与T细胞的免疫调节相关，其主要通过降解外周细胞中的色氨酸发挥调节作用。色氨酸是一种必需氨基酸，是所有生命合成蛋白的一种重要原料并参与其它重要的代谢功能。本文将对IDO的免疫调节的机制最新进展做一综述。

吲哚胺2,3-双加氧酶(IDO)参与抑郁症发病机制的研究进展

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。

吲哚胺2,3-双加氧酶(IDO)的色胺酮类抑制剂筛选及其体外抗肿瘤作用

目的评价色胺酮衍生物吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)的抑制活性,并研究其作为IDO抑制剂的抗肿瘤作用。方法采用基因工程手段表达、纯化重组人IDO(rhIDO),建立IDO活性检测体系;以色胺酮衍生物作为对象,进行IDO抑制活性初筛,对抑制类型、半数抑制浓度以及抑制常数进行测定;构建高表达人IDO的pcDNA3.1(+)-hIDO转染HEK 293细胞,评价色胺酮衍生物在细胞水平上的IDO抑制活性;采用MTT比色法考察色胺酮衍生物3对人非小细胞肺癌A549细胞的生长抑制作用。结果 6个被测色胺酮衍生物均具有IDO抑制活性,且细胞水平上的抑制效力高于酶活水平,抑制效力均优于目前通用的IDO抑制剂1-甲基色氨酸(1-methyl-tryptophan,1-MT)。色胺酮衍生物3作为最强的IDO抑制剂,其Ki值为0.161μmol/L。MTT实验结果显示,色胺酮衍生物3显著抑制A549细胞生长,IC50为8.77μmol/L。结论色胺酮衍生物是一类新型高效的IDO抑制剂,在体外对A549细胞具有较强的抗肿瘤活性。

Foxp3^(+)Treg和IDO^(+)APC细胞在不同病变宫颈组织中的表达

目的:检测免疫抑制细胞Foxp3^(+)Treg和免疫蛋白IDO在不同病变宫颈组织中的表达情况。方法:采用免疫细胞化学及蛋白印记(Western blot)检测Foxp3蛋白及IDO蛋白在宫颈癌细胞系HeLa、SiHa及C33A中的表达与分布;采用免疫组织化学法检测Foxp3和IDO在20例正常宫颈组织及45例不同程度宫颈病变组织中的表达情况。结果:Foxp3蛋白在HeLa、SiHa及C33A中无表达;IDO蛋白在HeLa、SiHa及C33A细胞的胞浆中均有表达。Foxp3蛋白在宫颈组织中表达于Treg,IDO蛋白在宫颈组织中表达于APC和/或异常细胞。宫颈病变组织中的Foxp3^(+)Treg(H=43.211,P=0.000)和IDO蛋白的表达均明显高于正常组织(χ^(2)=20.028,P=0.00;Z=226.600,P=0.00)。随着病理级别升高,Foxp3^(+)Treg的侵袭性(H=28.307,P=0.000)增加,Foxp3^(+)Treg与IDO^(+)APC的数目显著正相关(rs=0.550,P=0.003)统计学正相关(rs=0.550,P=0.000)。结论:在宫颈癌进展的不同病理阶段,局部微环境中Foxp3^(+)Treg数目随宫颈细胞恶性转化的进程而增多,IDO^(+)APC细胞在早期宫颈病变组织中表达多于晚期病变。

Tryptophan 2,3-dioxygenase-positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine-mediated ferroptosis resistance of metastatic cells and T cell dysfunction

Background:Tumor metastasis is a major threat to cancer patient survival.The organ-specific niche plays a pivotal role in tumor organotropic metas-tasis.Fibroblasts serve as a vital component of the metastatic microenviron-ment,but how heterogeneous metastasis-associated fibroblasts(MAFs)promote organotropic metastasis is poorly characterized.Here,we aimed to decipher the heterogeneity of MAFs and elucidate the distinct roles of these fibroblasts in pulmonary metastasis formation in breast cancer.Methods:Mouse models of breast cancer pulmonary metastasis were estab-lished using an in vivo selection method of repeated injections of metastatic cells purified from the mouse lung.Single-cell RNA-sequencing(scRNA-seq)was employed to investigate the heterogeneity of MAFs.Transgenic mice were used to examine the contribution of tryptophan 2,3-dioxygenase-positive matrix fibroblasts(TDO2^(+)MFs)in lung metastasis.Results:We uncovered 3 subtypes of MAFs in the lung metastatic microenviron-ment,and their transcriptome profiles changed dynamically as lung metastasis evolved.As the predominant subtype,MFs were exclusively marked by platelet-derived growth factor receptor alpha(PDGFRA)and mainly located on the edge of the metastasis,and T cells were enriched around MFs.Notably,high MF sig-natures were significantly associated with poor survival in breast cancer patients.Lung metastases were markedly diminished,and the suppression of T cells was dramatically attenuated in MF-depleted experimental metastatic mouse mod-els.We found that TDO2^(+)MFs controlled pulmonary metastasis by producing kynurenine(KYN),which upregulated ferritin heavy chain 1(FTH1)level in dis-seminated tumor cells(DTCs),enabling DTCs to resist ferroptosis.Moreover,TDO2^(+)MF-secreted chemokines C-C motif chemokine ligand 8(CCL8)and C-C motif chemokine ligand 11(CCL11)recruited T cells.TDO2^(+)MF-derived KYN induced T cell dysfunction.Conditional knockout of Tdo2 in MFs diminished lung metastasis and enhanced immune activation.Conclusions:Our study reveals crucial roles of TDO2^(+)MFs in promoting lung metastasis and DTCs’immune evasion in the metastatic niche.It suggests that targeting the metabolism of lung-specific stromal cells may be an effective treatment strategy for breast cancer patients with lung metastasis.

脂质体介导pIDO-EGFP转染原代培养软骨细胞的初步研究

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。

IDO基因稳定转染HepG_2细胞系的建立

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。

清肠化瘀方治疗溃疡性结肠炎疗效及对IDO、Treg/Th17平衡的影响

【目的】观察清肠化瘀方治疗溃疡性结肠炎(ulcerative colitis,UC)的临床疗效,并探讨其治疗机制。【方法】将96例大肠湿热型活动期UC患者随机分为研究组和对照组,每组各48例。2组患者均给予美沙拉嗪肠溶片口服,研究组同时给予口服中药清肠化瘀方治疗,对照组同时给予口服清肠化瘀方低剂量配方颗粒(安慰剂,药物含量为试验药品的2.5%)治疗,2组疗程均为12周。观察2组患者治疗前后中医证候评分、改良Mayo评分、Baron内镜评分、血清吲哚胺2,3双加氧酶(IDO)、白细胞介素(IL)-10、转化生长因子β(TGF-β)、IL-17、IL-21水平和外周血调节性T淋巴细胞(Treg)、辅助性T细胞17(Th17)含量的变化情况,并比较2组患者的临床疗效(包括有效率和缓解率)及肠镜疗效(包括内镜应答率和黏膜愈合率)。【结果】(1)治疗12周后,研究组的临床有效率、临床缓解率、内镜应答率、黏膜愈合率分别为95.83%(46/48)、83.33%(40/48)、97.92%(47/48)、91.67%(44/48),对照组分别为75.00%(36/48)、60.42%(29/48)、79.17%(38/48)、70.83%(33/48),组间比较,研究组的临床有效率、临床缓解率、内镜应答率、黏膜愈合率均高于对照组(P<0.05或P<0.01)。(2)治疗后,2组患者的腹痛、腹泻、脓血便、里急后重等各项中医证候评分以及改良Mayo评分和Baron内镜评分均较治疗前明显降低(P<0.01),且研究组的降低作用均明显优于对照组(P<0.01)。(3)治疗后,2组患者的血清IDO、IL-17、IL-21水平和外周血Th17含量均较治疗前明显降低(P<0.01),血清IL-10、TGF-β水平和外周血Treg含量均较治疗前明显升高(P<0.01),且研究组对血清IDO、IL-17、IL-21水平和外周血Th17含量的降低作用以及对血清IL-10、TGF-β水平和外周血Treg含量的升高作用均明显优于对照组(P<0.01)。【结论】清肠化瘀方应用于大肠湿热型活动期UC的治疗,可有效改善患者中医证候,促进肠黏膜的修复和愈合,临床疗效和肠镜疗效更优,其机制可能与通过抑制IDO的高表达而调节Treg/Th17平衡有关。

敲低吲哚胺2,3双加氧酶2基因抑制荷黑素瘤小鼠肿瘤生长并增强其免疫功能

目的以吲哚胺2,3双加氧酶2(IDO2)作为治疗靶标,研究IDO2基因表达在肿瘤治疗中的作用及其对免疫应答的影响。方法采用B16-BL6细胞株构建小鼠黑素瘤种植模型,以携带IDO2小干扰RNA的质粒(IDO2-shRNA)及对照组质粒(scramble-shRNA)尾静脉高压注射法治疗小鼠黑素瘤;游标卡尺测量肿瘤大小;流式细胞术检测各组引流淋巴结内调节性T细胞(Treg)百分比、T细胞凋亡百分比,以及脾脏内树突状细胞(DC)表面共刺激分子CD80、CD86表达情况;乳酸脱氢酶法检测CD8+T淋巴细胞杀伤肿瘤细胞的能力;ELISA检测血清内肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)的水平。结果 IDO2-shRNA治疗组肿瘤的形成时间较晚,肿瘤的生长速度缓慢,离体肿瘤质量明显减少;IDO2-shRNA治疗组引流淋巴结内的Treg减少,T细胞凋亡降低,脾脏DC表面共刺激分子CD80、CD86明显增加;CD8+T细胞杀伤B16-BL6的能力增强,血清内TNF-α、IFN-γ表达水平升高。结论敲低荷瘤小鼠体内IDO2可抑制黑素瘤生长,提高机体的抗肿瘤免疫反应。

和厚朴酚抑制IDO1表达改善老年小鼠术后认知功能障碍的实验研究

目的探讨和厚朴酚对术后认知功能障碍防治作用的机制。方法将18月龄雄性C57BL/6小鼠随机分为4组:Control组(溶剂预处理7 d,不进行手术)、HNK组(10 mg/kg和厚朴酚预处理7 d,不进行手术)、Surgery组(溶剂预处理7 d,脾切除术建模)和Surgery+HNK组(10 mg/kg和厚朴酚预处理7 d,脾切除术建模)。运用Morris水迷宫评估空间记忆功能,免疫荧光染色观察海马凋亡神经元比例,检测海马Bcl-2、Bax、活化Caspase-3以及吲哚胺2,3双加氧酶1(indoleamine 2,3-dioxygenase 1,IDO1)表达水平,高效液相色谱检测色氨酸毒性代谢产物含量。结果与Surgery组相比,Surgery+HNK组水迷宫测试期第1、3、7天目标象限停留时间和平台穿越次数增加;术后第7天海马凋亡神经元比例降低;术后第1天Bcl-2表达增高、Bax表达水平降低、活化Caspase-3水平降低,IDO1表达降低;色氨酸毒性代谢物降低。结论和厚朴酚可通过抑制IDO1表达,调控色氨酸代谢,减轻海马神经元损伤,改善小鼠术后认知功能障碍。

吲哚胺2,3双加氧酶对人绒毛膜癌JEG-3细胞增殖及迁移能力的影响

目的观察吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygenase,IDO)对人绒毛膜癌JEG-3细胞体外增殖、迁移能力的影响。方法通过IDO抑制剂(1-L-MT)及短发夹RNA基因干扰抑制IDO表达,利用MTS增殖实验、Transwell迁移试验检测对细胞增殖和迁移能力的影响。结果基因敲减能明显降低IDO表达水平。1-L-MT和基因敲减的JEG-3细胞与对照组相比,细胞的增殖和迁移能力明显下降。结论抑制IDO能够降低绒癌细胞系JEG-3细胞的增殖和迁移能力。

吲哚胺2,3-双加氧酶与细胞因子信号传导抑制蛋白-3在妊娠期高血压疾病患者胎盘组织中的表达及相关性分析

目的:探究吲哚胺2,3-双加氧酶(IDO)与细胞因子信号传导抑制蛋白-3(SOCS3)在妊娠期高血压疾病(HDP)患者胎盘组织中的表达及其与疾病进展的相关性。方法:通过Western blot法检测HDP患者胎盘组织中IDO和SOCS3的表达,分析胎盘组织中两者的表达量及相关性。结果:HDP患者及正常妊娠者胎盘组织中均有IDO与SOCS3表达,IDO、SOCS3表达与HDP进展呈负相关。三组胎盘组织中IDO与SOCS3的表达均呈正相关,子痫前期组IDO与SOCS3相关性明显高于HDP组、正常妊娠组,HDP组IDO与SOCS3的相关性明显高于正常妊娠组。结论:IDO及SOCS3在妊娠晚期免疫耐受中起重要作用,且可能参与了HDP的发病过程,IDO与SOCS3表达及其相关程度可预示HDP的进展。

哈萨克族食管癌患者外周血IDO检测的临床意义

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。