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1.
目的探讨湖北汉族人肿瘤坏死因子-α(TNF-α)基因启动子多态性及其与慢性乙型肝炎易感性之间的关系。方法应用聚合酶链反应-限制性片段长度多态性分析方法(RFLP),检测126名正常对照者和131例慢性乙型肝炎患者TNF-α基因启动子多态性。结果共发现12种启动子基因型,以GG.GG.CC.CC、GG.GG.CC.CA、GG.GG.CT.CC和GG.GA.CC.CC基因型多见,约占85%;通过对TNF-α基因启动子4个位点基因型分析发现,慢性乙型肝炎患者和正常对照者TNF-α基因启动子-238G/A、-857C/T位点基因型分布频率差异无显著性,而-308G/A、-863C/A位点基因型分布频率差异有显著性。结论湖北汉族人慢性乙型肝炎易感性与TNF-α基因启动子-308G/A、-863C/A位点多态性有关,其中TNF-α-308GA、-863CA基因型携带者患慢性乙型肝炎风险相对较小。 相似文献
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目的探讨肿瘤坏死因子-α308位点基因多态性与牙周炎易感性的关系。方法采用序列特异引物PCR方法 (SSP-PCR)方法检测了78例重度慢性牙周炎(CP)患者和70例健康对照组的TNFα-308(G/A)位点基因多态性。结果 CP患者TNFα-308各基因型(GG,GA,AA)频率分别为70.5%、0%和29.5%,在对照者中分别为67%,3%和30%二组之间的基因型频率分布的比较,差异没有显著性(χ2=2.29,P〉0.05);GG和AA的等位基因频率在CP中分别85.3%和14.7%,在对照者中分别为82%和18%,二者之间比较,差异没有显著性(χ2=0.526,P〉0.05)。结论 TNF-α-308基因多态性位点可能不是中国人患牙周病的主要易感位点基因。 相似文献
3.
目的 探讨肿瘤坏死因子α(tumor necrosis factorα,TNF-α)基因启动子区-308G/A、-857C/T和-1031T/C位点,白细胞介素6(interleukin-6)基因启动子-174G/C和-572C/G多态性与精神分裂症发生的相关性.方法 采用聚合酶链反应-限制性片段长度多态性分析方法检测346例精神分裂症患者、323名健康对照各个多态性位点的基因型,采用SPSS 13.0进行统计学分析.结果 TNF-α基因-857C/T位点的基因型及等位基因频率分布在精神分裂症组与正常对照组均存在统计学意义(P<0.05),其中,-857T的等位基因的频率在精神分裂症组均显著高于对照组(x2=9.414,P=0.002,OR=1.511,95%CI:1.160~1.969).-857C/T位点不同基因型患者之间的阳性和阴性症状量表总分及阴性症状差异存在显著性,且TT基因型的分值显著高于CC基因型(P<0.05).结论 TNF-α基因-857C/T位点可能与精神分裂症的发病存在关联,其中,-857T等位基因可能是易感基因,并且-857C/T位点与阳性和阴性症状量表评分中阴性症状存在关联. 相似文献
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目的 探讨肿瘤坏死因子水平及TNFα-850C/T基因多态性与变应性鼻炎的关系.方法 用放免法测定TNF水平,运用多聚酶链反应技术检测90名无亲缘关系的尘螨变应性鼻炎患者和107名无血缘关系的健康汉族人肿瘤坏死因子TNFα-85(C/T基因多态性.结果 变应性鼻炎组肿瘤坏死因子TNFα-850 C/C、T/C、T/T表型频率分别为:0.7445、0.2333、0.0222,对照组分别为0.7850、0.1963、0.0187;变应性鼻炎组TNFα-850 C、TNFα-850T基因频率分别为:0.8611、0.1389,对照组分别为:0.8832、0.1168;TNFα-850C/T各种基因型频率在变应性鼻炎组与正常对照组之间差异无统计学意义(P>0.05).而血浆中TNF水平,变应性鼻炎组明显高于对照组,两组之间比较差异有统计学意义(P<0.05).结论 血清TNF水平显著升高,提示炎性反应在变应性鼻炎病程中有重要作用,肿瘤坏死因子TNFα-850C/T基因多态性与变应性鼻炎无明显相关. 相似文献
6.
为探讨TNFα-863 C/A基因多态性与阿尔茨海默病(AD)的关系,采用聚合酶链式反应—限制性片段长度多态性(PCR-RFLP)技术检测66例AD患者(AD组)和119名正常人(对照组)的TNFα-863 C/A基因多态性。结果表明,AD组TNFα-863 C/C、C/A、A/A表型频率分别为:0.9242、0.0758、0,对照组为0.7563、0.2446、0;AD组TNFα-863 C、TNFα-863A基因频率分别为:0.9621、0.0379,对照组分别为:0.8782、0.1218;TNFα-863 C/A基因表型频率在AD组与对照组差异有统计学意义(P〈0.05)。因此TNFα-863 C/A基因多态性与AD有明显相关性。 相似文献
7.
目的研究中国广东汉族人群中血清、脑脊液(cerebrospinalfluid,CSF)肿瘤坏死因子-α(tumornecrosisfactor-α,TNF-α)水平及其-308G/A基因多态性与多发性硬化之间的相关性。方法采用双抗体夹心ABC-ELISA法测定68例无亲缘关系的急性发作期多发性硬化(multiplesclerosis,MS)患者和55例非免疫系统疾病患者的血清、CSF的TNF-α水平,同时应用聚合酶链反应-限制性片段长度多态性技术检测上述68例MS患者和106名无血缘关系的广东籍健康汉族人的TNF-α-308G/A基因型。结果发作期MS患者血清中TNF-α水平与非免疫系统疾病患者组间差异有统计学意义(P<0·05),分别是(276±71)pg/mL和(234±76)pg/mL;发作期MS患者CSF中TNF-α水平与非免疫系统疾病患者组差异无统计学意义(P>0·05),分别是(265±78)pg/mL和(245±83)pg/mL;TNF-α-308G/A各等位基因型频率在MS组和正常人组比较差异无统计学意义(P>0·05),MS组TNF-α基因AA基因型和A等位基因频率分别为4.4%和14·0%,正常人对照组分别为0和8.5%。结论(1)发作期MS与血清中TNF-α水平相关,与CSF中TNF-α水平不相关。(2)从目前调查的例数中,中国广东汉族人群TNF-α基因-308G/A多态性与广东人群中MS不相关。 相似文献
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目的探讨肿瘤坏死因子α基因多态性与强直性脊柱炎(AS)发生的易感关系。方法采用序列特异引物PCR方法(SSP-PCR)检测了136例AS患者和127例正常人的TNF-α5旁侧-857C/T,-863C/A和-1031T/C三个基因多态性位点,并比较了部分不同地区人群之间的基因型与等位基因频率。结果AS患者TNF-α-857基因型(CC,TC和TT)分布频率分别是64.0%,35.3%和0.7%;TNF-α-863基因型(CC,CA和AA)分布频率分别是68.4%,30.0%和1.5%;TNF-α-1031基因型(TT,TC和CC)分布频率分别是66.2%,32.4%和1.5%;TNF-α-857等位基因频率C和T分别是81.6%和18.8%;TNF-α-863等位基因频率C和A分别是83.5%和16.5%;TNF-α-1031等位基因频率T和C分别是:82.4%和17.6%;正常对照者TNF-α-857基因型(CC,TC和TT)分布频率分别是70.9%,27.6%和1.6%;TNF-α-863基因型(CC,CA和AA)分布频率分别是68.5%,29.9%和1.6%;TNF-α-1031基因型(TT,TC和CC)分布频率分别是69.3%,29.1%和1.6%;TNF-α-857等位基因频率C和T分别是84.6%和15.4%;TNF-α-863等位基因频率C和A分别是83.5%和16.5%;TNF-α-1031等位基因频率T和C分别是:83.9%和16.1%;AS患者和正常对照者之间的基因型分布和等位基因频率比较差异无显著性,(P>0.05);本文中国汉族人TNF-α-857(C/T),-863(C/A),-1031(T/C)位点基因多态性分布同亚洲的日本、韩国人群基本一致,差异无显著性;-863(C/A),-1031(T/C)位点基因多态性分布同欧洲的英国、荷兰、瑞典人群比较差异也无显著性,但欧洲人群的TNF-α-857T的等位基因频率明显高于亚洲人群,差异有显著性(P<0.05)。结论TNF-α-857,-863和-1031三个基因多态性位点可能不是中国人患AS的主要易感位点基因。 相似文献
9.
目的 探讨肿瘤坏死因子(TNF)α-238及TNFα-308基因多态性与动脉硬化性脑梗死的关系.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测97例动脉硬化性脑梗死(CI组)及141例正常人(对照组)的外周血TNFα-238、TNFα-308基因多态性AA、AG、GG的基因型.结果 CI组TNFα-238 GG、GA和AA基因型频率分别为88.66%、11.34%和0;对照组分别为95.74%、4.26%和0.CI组TNFα-238 G、TNFα-238 A基因频率分别为94.33%、5.67%;对照组分别为97.87%、2.13%.TNFα-238各种基因型频率在CI组与正常对照组之间的差异有统计学意义(均为P<0.05).CI组TNFα-308 GG、GA和AA基因型频率分别为77.32%、8.25%和14.43%;对照组分别为92.20%、5.67%和2.13%.CI组TNFα-308 G、TNFα-308 A基因频率分别为81.44%、18.56%;对照组分别为95.04%、4.96%.TNFα-308各种基因型频率在CI组与正常对照组之间的差异有统计学意义(均为P<0.05).结论 TNFα-238和TNFα-308基因多态性AA、AG、GG基因型与CI有关联. 相似文献
10.
目的了解轻度认知功能障碍与TNFα-850 C/T基因多态性的相关性。方法使用PCR方法检测119名正常人(正常对照组)及100例轻度认知功能障碍(MCI)的TNFα-850 C/T基因单核苷酸多态性。结果正常对照组TNFα-850 C/T的C/C、C/A、A/A表型频率分别为0.7899、0.1681、0.042,MIC组分别为0.7700、0.1800、0.0500;正常对照组TNFα-850 C/T的C、A基因频率分别为0.8739、0.1261,MIC组分别为0.8600、0.1400;在与正常对照组相比,MIC组TNFα-850 C/T各种基因型频率差异无统计学意义(P﹥0.05)。结论从目前调查的例数来看,轻度认知功能障碍与TNFα-850 C/T基因多态性不存在明显相关性。 相似文献
11.
Mirahmadian M Kalantar F Heidari G Safdarian L Mansouri R Amirzargar AA 《American journal of reproductive immunology (New York, N.Y. : 1989)》2008,60(2):179-185
PROBLEM: Considering that certain cytokines may change during pre-eclampsia (PE), because of functional polymorphisms in their genes, our purpose was to determine the association between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) gene polymorphisms and development of PE. METHOD OF STUDY: The genetic polymorphisms of TNF-alpha and IL-10 was studied by polymerase chain reaction-sequence specific primers in the DNA of peripheral blood cell from 160 patients with PE and 100 healthy pregnant women. RESULTS: We found a significant difference between TNF-alpha A allele (-308) and G allele (-238) in PE patients compared with those of the control groups. A significantly higher C/C genotype frequency of IL-10 (-592 and -819) was observed in the PE patients than in the control groups. In addition, the frequencies of three common IL-10 haplotypes (GCC, ACC, and ATA) did not show any significant difference between the study groups. CONCLUSION: These findings would support the concept of contribution of TNF-alpha and IL-10 gene polymorphisms in the pathogenesis of PE in our population. 相似文献
12.
H. Hohjoh T. Nakayama J. Ohashi T. Miyagawa H. Tanaka T. Akaza Y. Honda T. Juji K. Tokunaga 《Tissue antigens》1999,54(2):138-145
Narcolepsy is a sleep disorder in which multiple factors, including environmental and genetic factors, are involved. A genetic factor strongly associated with the disorder has been found in the human leukocyte antigen (HLA) class II region: the haplotype, DRB1*1501-DQB1*0602, predisposes to narcolepsy. No susceptibility genes other than the HLA-haplotype have been found. In this paper, we performed an association study of the tumor necrosis factor-alpha (TNF-alpha) gene located in the HLA class III region with human narcolepsy, in which we examined the known single-nucleotide polymorphisms (SNPs) in the promoter region in 49 narcoleptic patients, who were all positive for DRBI*1501, and 111 healthy control individuals. The results indicated that the frequency of the genotype at position -857 (-857SNP) was significantly different between the patients and controls, and the allele frequencies of 857SNP revealed that the frequency of -857T was significantly increased in the patients as compared with that in the controls (P=0.0068). In addition, haplotypes presumed from HLA-DRB1, -857SNP and HLA-B loci suggested that -857T was mainly associated with DRB1 alleles other than DRB1*1501: the significant increase in frequency of -857T in the patients was not caused by allelic association with DRB1*1501. Therefore, it is conceivable that the TNF-alpha with 857T was associated with narcolepsy independently of the strong association of DRB1*1501 with the disorder. Altogether, the data presented here lead us to propose that TNF-alpha could be a new susceptibility gene in human narcolepsy. 相似文献
13.
Krikovszky D Vásárhelyi B Tóth-Heyn P Körner A Tulassay T Madácsy L 《Clinical genetics》2002,62(6):474-477
Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine, which also influences blood pressure (BP). The G-308A polymorphism of the TNF-alpha gene is associated with altered TNF-alpha production. The prevalence of the TNF-alpha-308A allele is reportedly higher among patients with type 1 diabetes mellitus (T1DM) than in the healthy population. In this study we investigated whether this genetic polymorphism might correlate with BP values in diabetic adolescents. Ambulatory BP monitoring (ABPM) was performed in 126 adolescents with T1DM (mean age: 14 +/- 2.4 years). The TNF-alpha G-308A genotype was determined by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methodologies. ABPM results were related to healthy reference values and are given as standard deviation score (SDS). The prevalence of the -308A allele was higher in diabetic adolescents than the Hungarian reference population (0.26 vs 0.14, p < 0.01). TNF-alpha genotype was associated both with systolic and diastolic BP values (p < 0.01 and p < 0.01, respectively). In patients with TNF-alpha-308GG and -308GA/AA genotypes, the 24-h systolic BP average values were 0.37 +/- 1.33 and -0.38 +/- 1.28 SDS, while 24-h diastolic BP average values were 0.09 +/- 1.30 and -0.67 +/- 1.31 SDS. Hence, the TNF-alpha-308A allele carrier state appears to be associated with lower systolic and diastolic BP values. 相似文献
14.
TNF-α在热疗降低胶质瘤侵袭性过程中的作用 总被引:1,自引:0,他引:1
目的 探讨肿瘤坏死因子-α(TNF-α)在热疗抑制肿瘤侵袭性过程中的作用。方法 热处理大鼠恶性胶质瘤细胞(C6细胞)和胶质瘤大鼠后,放射免疫法监测培养液和脑胶质瘤组织内TNF-α的浓度;免疫组化法检测经热疗/ TNF-α/生理盐水处理过的胶质瘤组织内增殖细胞核抗原(PCNA)蛋白的表达。利用Transwell构建肿瘤侵袭模型,通过结晶紫染色法检测肿瘤侵袭性。电镜观察C6恶性胶质瘤大鼠肿瘤血管内皮细胞的凋亡。结果 热疗可增加C6细胞培养液和胶质瘤大鼠肿瘤组织内的TNF-α含量及降低胶质瘤侵袭性,均于热疗后120min时达高峰(P<0.01)。热疗与TNF-α单独作用于胶质瘤大鼠后,均可引起胶质瘤大鼠肿瘤血管内皮细胞的凋亡。且TNF-α引起内皮细胞的凋亡水平与热处理后C6细胞培养液中TNF-α含量一致。结论 热疗可能是通过增加TNF-α引起肿瘤血管内皮细胞凋亡而抑制了肿瘤侵袭性。 相似文献
15.
Polymorphism of promotor sites of interleukins-4 and -10 and tumor necrosis factor-alpha genes in HIV-infected patients 总被引:2,自引:0,他引:2
The distribution of allele variants of promotor sites of interleukins 4 (C-590T) and 10 (C-597A) and tumor necrosis factor-alpha (G-308A) genes was studied in HIV-infected patients and normal subjects of the Europeoid population in Russia. Some deviations in the distribution of genotypes of the studied polymorphism were revealed in HIV-infected patients compared to the control. The distribution of genotypes in these groups is different for men and women, which is significant for inheritance of allele variants of the cytokine gene. 相似文献
16.
Blömeke B Brans R Dickel H Bruckner T Erdmann S Heesen M Merk HF Coenraads PJ 《Allergy》2009,64(2):279-283
Background: Para -phenylenediamine (PPD) and related chemicals are common contact sensitizers, frequently causing allergic contact dermatitis (ACD). The cytokine tumor necrosis factor-alpha (TNF-α) plays a key role in contact sensitization.
Methods: In this case–control study, we evaluated the distribution of variations in the regulatory region of the gene for TNF-α ( TNFA-308 G/A ) in 181 Caucasian individuals with a history of ACD and sensitization to PPD and 161 individuals with no history of sensitization to PPD.
Results: The frequency of GA or AA TNFA genotypes was significantly higher in individuals sensitized to PPD than in age- and gender-matched controls giving an odds ratio (OR) of 2.16 (95% confidence interval, CI: 1.35–3.47; P = 0.0016). This relation was even more pronounced when restricting cases to females over 45 years (OR = 3.71; 95% CI: 1.65–8.31; P = 0.0017) vs younger females (less than or equal to 45 years; OR = 2.41; 95% CI: 1.03–5.65; P = 0.044) or males (OR = 1.05; 95% CI: 0.449–2.47; P = 1.0). In addition, a logistic regression model revealed a significant effect for TNFA-308 AA and AG vs GG genotype (point estimate = 2.152; 95% Wald CI: 1.332–3.477).
Conclusions: These findings suggest a possible role for the TNFA-308 genetic polymorphism as a susceptibility factor for chemically induced ACD. 相似文献
Methods: In this case–control study, we evaluated the distribution of variations in the regulatory region of the gene for TNF-α ( TNFA-308 G/A ) in 181 Caucasian individuals with a history of ACD and sensitization to PPD and 161 individuals with no history of sensitization to PPD.
Results: The frequency of GA or AA TNFA genotypes was significantly higher in individuals sensitized to PPD than in age- and gender-matched controls giving an odds ratio (OR) of 2.16 (95% confidence interval, CI: 1.35–3.47; P = 0.0016). This relation was even more pronounced when restricting cases to females over 45 years (OR = 3.71; 95% CI: 1.65–8.31; P = 0.0017) vs younger females (less than or equal to 45 years; OR = 2.41; 95% CI: 1.03–5.65; P = 0.044) or males (OR = 1.05; 95% CI: 0.449–2.47; P = 1.0). In addition, a logistic regression model revealed a significant effect for TNFA-308 AA and AG vs GG genotype (point estimate = 2.152; 95% Wald CI: 1.332–3.477).
Conclusions: These findings suggest a possible role for the TNFA-308 genetic polymorphism as a susceptibility factor for chemically induced ACD. 相似文献
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Association of tumor necrosis factor-{alpha} gene polymorphisms with advanced stage endometriosis 总被引:2,自引:0,他引:2
Lee GH Choi YM Kim SH Hong MA Oh ST Lim YT Moon SY 《Human reproduction (Oxford, England)》2008,23(4):977-981
BACKGROUND: This study was performed to investigate whether specific haplotypesand several single nucleotide polymorphisms in the promoterregion of the tumor necrosis factor (TNF)- gene are associatedwith the risk of advanced stage endometriosis in a Korean population. METHODS: This study comprised women with (n = 246) or without (n = 248)endometriosis. The TNF:g.[-1031T > C], TNF:g.[-863C >A] and TNF:g.[-857C > T] polymorphism in the TNF- gene wereassessed by PCR-restriction fragment length polymorphism analysis,which utilized digestion by BbsI, HypCH4IV and HypCH4IV restrictionenzymes, respectively. In silico haplotypes were deduced byusing the Haploview version 3.32. RESULTS: The genotype distribution of TNF:g.[-1031T > C] was significantlydifferent between total endometriosis patients and the controls(T/T of 56.9 versus 60.1%, T/C of 35.4 versus 37.5% and C/Cof 7.7 versus 2.4%, respectively, P = 0.027). This differenceat the TNF:g.[-1031T > C] tends to increase in Stage IV endometriosis(P = 0.01). However, there was no difference in the TNF:g.[-863C> A] and TNF:g.[-857C > T] site between the two groups.Even when the endometriosis cases were subdivided into AmericanSociety for Reproductive Medicine Stages III and IV, genotypedifferences were not found. The CC homozygote at TNF:g.-863was more frequently found in the controls than Non-CC group(P = 0.04; odds ratio = 0.67; 95% confidence interval = 0.45–0.98).All haplotypes and diplotypes, deduced by in silico analysis,showed no association with subgroups or controls. CONCLUSIONS: Our results suggest that the genotype frequencies at the TNF:g.[-1031T> C] and the TNF:g.[-863C > A] sites may be associatedwith advanced stage endometriosis in the Korean population. 相似文献
18.
目的通过对紫绀型先天性心脏病和非紫绀型先天性心脏病患者围体外循环(CPB)期血清促红细胞生成素(EPO)、TNF-α水平的变化进行动态观察,探讨EPO对围体外循环期炎症因子水平可能的影响。方法 40例先天性心脏病患儿,其中紫绀组和非紫绀组各20例,均在中低温体外循环下接受心内直视手术,分别于麻醉后、CPB 30 min、CPB后2 h、CPB后24 h取血,测定并比较两组患者的血清EPO和TNF-α水平变化。结果紫绀组在CPB 30 min的血清TNF-α明显低于非紫绀组(P〈0.05),在CPB后2 h、CPB后24 h的血清TNF-α高于非紫绀组(P〈0.01,P〈0.05);术前血清EPO水平与CPB 30 min时血清TNF-α水平呈负相关(P〈0.05)。结论紫绀型先天性心脏病可能存在某种适应性改变,可在一定程度抑制CPB后的全身炎症反应,其抗炎症作用机制可能与EPO相关。 相似文献
19.
The tumor necrosis factor-alpha promoter -1031C polymorphism is associated with decreased risk of endometriosis in a Japanese population 总被引:3,自引:0,他引:3
Asghar T Yoshida S Kennedy S Negoro K Zhuo W Hamana S Motoyama S Nakago S Barlow D Maruo T 《Human reproduction (Oxford, England)》2004,19(11):2509-2514
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional proinflammatory cytokine, associated with various inflammatory and autoimmune diseases. Elevated TNF-alpha levels in peritoneal fluid have been reported in women with endometriosis, suggesting that TNF-alpha may be involved in the development of endometriosis. In this study, we investigated the possible association between endometriosis and the TNF-alpha gene promoter polymorphisms -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C in a Japanese population. METHODS: We compared the distribution of the -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C polymorphisms in the promoter region of TNF-alpha in 130 endometriosis cases and 185 controls using PCR-RFLP analysis. RESULTS: The allele frequencies of -238A, -308A, -857T, -863A and -1031C in controls were 2.0%, 1.3%, 19.4%, 17.0% and 18.6%, and in the cases 1.1%, 0.3%, 19.6%, 18.6% and 13.6%, respectively. No significant differences in frequencies were found between the crude endometriosis cases and controls. However, when the endometriosis group was divided into a subgroup of women with stage IV disease only, the frequency of the -1031C allele was significantly lower in this subgroup than controls. CONCLUSIONS: The variability of the -1031T/C polymorphism of the TNF-alpha gene may be associated with susceptibility to (AUTHOR: as meant?) endometriosis. 相似文献
20.
Jose M. Alvaro-Gracia Caroline Yu Nathan J. Zvaifler Gary S. Firestein 《Journal of clinical immunology》1993,13(3):212-218
We recently described mutual antagonism between IFN-gamma and TNF-alpha on human fibroblast-like synoviocytes (FLS). TNF-alpha inhibits IFN-gamma-induced HLA-DR expression and IFN-gamma blocks TNF-alpha-dependent synoviocyte proliferation, collagenase production, and GM-CSF secretion. To study the mechanism of antagonism we have analyzed the effect these factors on the expression of cytokine surface receptors.125I-Labeled cytokine binding was measured on cultured FLS and the results were analyzed by Scatchard plots. Unstimulated synoviocytes expressed 9300 ± 1560 IFN-gamma binding sites per cell. A single class of high-affinity receptor was observed (K
d=4.5±2.5×10–10
M). TNF-alpha did not competitively inhibit125I-IFN-gamma binding. When FLS were incubated with TNF-alpha (100 ng/ml), there was a paradoxical 49.5 ± 5.6% increase in the number of binding sites for IFN-gamma (P=0.001), with no change in theK
d. Unstimulated FLS also expressed 2850 ± 700 TNF-alpha receptors per cells, with a singleK
d consistent with the lower-affinity TNF-alpha receptor (7.4±0.2×10–10
M). IFN-gamma did not directly interfere with TNF-alpha binding. Preincubation of FLS with 100 U/ml of IFN-gamma resulted in a 28.9 ± 9.0% increase in TNF-alpha receptor expression (P<0.008), with no change in theK
d. Low levels of the soluble 55-kD TNF receptor were detected in FLS supernatants. IFN-gamma did not effect soluble TNF receptor production. These data are the first demonstration of IFN-gamma and TNF-alpha receptors on FLS and show that TNF-alpha and IFN-gamma increase the expression of each other's receptor. Therefore the mutual antagonism between these two cytokines must occur through a postreceptor mechanism. 相似文献