趋化因子CXCL10与儿童自身免疫性甲状腺疾病
摘要
目的:观察血清趋化因子CXCL10的水平在AITD患儿(包括GD和HT)不同病程的变化情况,研究血清CXCL10的水平与甲状腺功能(FT3、FT4、sTSH)和甲状腺自身抗体(TGAb、TMAb、TRAb、TSI)指标之间的关系,探讨趋化因子CXCL10在儿童AITD的发病机制和病程中的作用。
方法:天津医科大学总医院儿科内分泌门诊AITD病例(其中包括57例GD病人和53例HT病人)及30例正常对照组儿童,收集他们的临床资料和血清。测定所有患儿和正常对照组的甲状腺功能和甲状腺自身抗体的水平,并采用ELSIA方法测定所有患儿和正常对照组的血清CXCL10的水平。比较三组(GD组、HT组和正常对照组)血清CXCL10的水平。把GD和HT病人分为新发病组、未缓解组及缓解组,比较各组及每组与正常对照组之间血清CXCL10的水平;比较24例GD患儿经甲巯咪唑治疗前后血清CXCL10的水平。相关分析AITD患儿血清CXCL10水平与甲状腺功能及甲状腺自身抗体水平的关系。
结果:
1儿童GD病人中血清CXCL10的水平高于正常对照组(P＜0.01)。儿童HT病人中血清CXCL10的水平高于正常对照组(p＜0.05)。GD组的血清CXCL10的水平高于HT组(p＜0.05)。
2 GD组儿童GD新发病组、未缓解组的血清CXCL10的水平高于缓解组(p＜0.001)和正常对照组(p＜0.001);新发病组与未缓解组的血清CXCL10的水平比较差别无统计学意义(p＞0.05);缓解组和正常对照组血清CXCL10的水平比较差别无统计学意义(p＞0.05);24例GD患儿,经甲巯咪唑治疗后血清CXCL10水平较治疗前下降,差别有统计学意义(p＜0.001)。GD组血清CXCL10水平与甲功指标FT3、FT4呈正相关(p＜0.05),与sTSH无相关性,与甲状腺自身抗体指标TGAb、TMAb、TRAb无相关性;与TSI呈正相关(p＜0.05)。
3 HT组儿童HT新发病组血清CXCL10的水平比缓解期和正常对照组升高(p＜0.001),未缓解期血清CXCL10的水平比缓解期和正常对照组升高(p＜0.05)新发病组与未缓解组的血清CXCL10的水平比较差别无统计学意义(p＞0.05);缓解组和正常对照组血清CXCL10的水平比较差别无统计学意义(p＞0.05)。HT组血清CXCL10的水平与sTSH呈正相关,与甲功指标FT3、FT4无相关,与甲状腺自身抗体指标TGAb、TMAb、TRAb、TSI无相关性。
结论:
1自身免疫性甲状腺疾病患儿CXCL10均高于正常对照组,说明趋化因子CXCL10参与儿童AITD发生发展的免疫调控。
2趋化因子CXCL10在儿童AITD的发病早期和复发期升高,在儿童AITD缓解后降低。说明趋化因子CXCL10在儿童AITD的发病早期起重要作用,并与疾病的严重程度密切相关,可以作为预测儿童AITD的疾病活动性的指标之一。
Objective:To observe the change of serum chemokine CXCL10 in children with AITD including Graves' Disease.(GD) and Hashimotos thyroiditis(HT) when they were in different course of disease.To study the relationship between the level of serum chemokine CXCL10 and the level of function of thyroid(FT3、FT4、sTSH) and the relationship between the level of serum chemokine CXCL10 and the level of thyroid antibody(TGAb、TMAb、TRAb、TSI),and then explore the role of chemokine CXCL10 in children with AITD when they were inatial stage and different course.
Methods:The children AITD cases of Tianjin medical university hospital pediatric endocrine clinic and their serum were random collected from January 2008 to January 2009,which included 53 cases with HT and 57 cases with GD and 30 controls.To determinate the level of function of thyroid and the level of thyroid antibody.To determinate their serum level of CXCL10 by ELISA method.To compare their serum levels of CXCL10 among three groups.To compare the serum level of CXCL10 in HT and GD when they were patients onset、non-remission and remission and controls;To compare the serum level of CXCL10 in 24 patients with GD when they were before therapied by MMI and therapied after 3-6 months.Make relationship analysis between the level of CXCL10 and the level of FT3、FT4、sTSH、TGAb、TMAb、TRAb、TSI in GD and HT.
Results:
1(1) The level of serum CXCL10 in 57 patients with GD was significant higher than controls(p＜0.001).(2) The level of serum CXCL10 in 53 patients with HT was significant higher than controls(p＜0.05).(3) The level of serum CXCL10 in GD was significant higher than HT(p＜0.05).
2 GD group The level of serum CXCL10 in GD when they were patients onset、non-remission was significant higher than they were remission(p＜0.001) and controls(p＜0.001).There was no difference between patients onset and non-remission(p＞0.05).There was no difference between patients remission and controls(p＞0.05).The level of serum CXCL10 in 24 patients with GD before they therapied was significant higher than they were therapied by MMI after 3-6 months (p＜0.001).In GD group there was positive correlation between CXCL10 and FT3、FT4;there was no correlation between CXCL10 and TSH;there was no correlation in GD group between CXCL10 and TGAb、TMAb、TRAb,there was positive correlation between CXCL10 and TSI(p＜0.05).
3 HT group The level of serum CXCL10 in HT when they were patients onset was significant higher than they were remission and controls(p＜0.001).The level of serum CXCL10 in HT when they were patients non-remission was significant higher than they were remission and controls(p＜0.05).There was no difference between patients onset and non-remission(p＞0.05).There was no difference between patients remission and controls(p＞0.05).In HT group there was positive correlation between CXCL10 and sTSH(p＜0.01),there was no correlation between CXCL10 and FT3、FT4(p＞0.05);there was no correlation between CXCL10 and TGAb、TMAb、TRAb、TSI(p＞0.05).
Conclusion:
1 The level of serum chemokines CXCL10 in children AITD was higher than controls, so this study supporting that chemokines CXCL10 may participate in the immunoregulation of children AITD when they were invasion and development.
2 The circulating concentrations of CXCL10 have been found to be increased in GD and HT when they were initial stage and relapses,and they have been found to be decreased in AITD when they were remission.CXCL10 play an important role in the initial stage of children with AITD.,and there was close correlation between CXCL10 and the severity degree of disease.So CXCL10 may be as one of index to predict the reactiveness of disease.
方法:天津医科大学总医院儿科内分泌门诊AITD病例(其中包括57例GD病人和53例HT病人)及30例正常对照组儿童,收集他们的临床资料和血清。测定所有患儿和正常对照组的甲状腺功能和甲状腺自身抗体的水平,并采用ELSIA方法测定所有患儿和正常对照组的血清CXCL10的水平。比较三组(GD组、HT组和正常对照组)血清CXCL10的水平。把GD和HT病人分为新发病组、未缓解组及缓解组,比较各组及每组与正常对照组之间血清CXCL10的水平;比较24例GD患儿经甲巯咪唑治疗前后血清CXCL10的水平。相关分析AITD患儿血清CXCL10水平与甲状腺功能及甲状腺自身抗体水平的关系。
结果:
1儿童GD病人中血清CXCL10的水平高于正常对照组(P＜0.01)。儿童HT病人中血清CXCL10的水平高于正常对照组(p＜0.05)。GD组的血清CXCL10的水平高于HT组(p＜0.05)。
2 GD组儿童GD新发病组、未缓解组的血清CXCL10的水平高于缓解组(p＜0.001)和正常对照组(p＜0.001);新发病组与未缓解组的血清CXCL10的水平比较差别无统计学意义(p＞0.05);缓解组和正常对照组血清CXCL10的水平比较差别无统计学意义(p＞0.05);24例GD患儿,经甲巯咪唑治疗后血清CXCL10水平较治疗前下降,差别有统计学意义(p＜0.001)。GD组血清CXCL10水平与甲功指标FT3、FT4呈正相关(p＜0.05),与sTSH无相关性,与甲状腺自身抗体指标TGAb、TMAb、TRAb无相关性;与TSI呈正相关(p＜0.05)。
3 HT组儿童HT新发病组血清CXCL10的水平比缓解期和正常对照组升高(p＜0.001),未缓解期血清CXCL10的水平比缓解期和正常对照组升高(p＜0.05)新发病组与未缓解组的血清CXCL10的水平比较差别无统计学意义(p＞0.05);缓解组和正常对照组血清CXCL10的水平比较差别无统计学意义(p＞0.05)。HT组血清CXCL10的水平与sTSH呈正相关,与甲功指标FT3、FT4无相关,与甲状腺自身抗体指标TGAb、TMAb、TRAb、TSI无相关性。
结论:
1自身免疫性甲状腺疾病患儿CXCL10均高于正常对照组,说明趋化因子CXCL10参与儿童AITD发生发展的免疫调控。
2趋化因子CXCL10在儿童AITD的发病早期和复发期升高,在儿童AITD缓解后降低。说明趋化因子CXCL10在儿童AITD的发病早期起重要作用,并与疾病的严重程度密切相关,可以作为预测儿童AITD的疾病活动性的指标之一。
Objective:To observe the change of serum chemokine CXCL10 in children with AITD including Graves' Disease.(GD) and Hashimotos thyroiditis(HT) when they were in different course of disease.To study the relationship between the level of serum chemokine CXCL10 and the level of function of thyroid(FT3、FT4、sTSH) and the relationship between the level of serum chemokine CXCL10 and the level of thyroid antibody(TGAb、TMAb、TRAb、TSI),and then explore the role of chemokine CXCL10 in children with AITD when they were inatial stage and different course.
Methods:The children AITD cases of Tianjin medical university hospital pediatric endocrine clinic and their serum were random collected from January 2008 to January 2009,which included 53 cases with HT and 57 cases with GD and 30 controls.To determinate the level of function of thyroid and the level of thyroid antibody.To determinate their serum level of CXCL10 by ELISA method.To compare their serum levels of CXCL10 among three groups.To compare the serum level of CXCL10 in HT and GD when they were patients onset、non-remission and remission and controls;To compare the serum level of CXCL10 in 24 patients with GD when they were before therapied by MMI and therapied after 3-6 months.Make relationship analysis between the level of CXCL10 and the level of FT3、FT4、sTSH、TGAb、TMAb、TRAb、TSI in GD and HT.
Results:
1(1) The level of serum CXCL10 in 57 patients with GD was significant higher than controls(p＜0.001).(2) The level of serum CXCL10 in 53 patients with HT was significant higher than controls(p＜0.05).(3) The level of serum CXCL10 in GD was significant higher than HT(p＜0.05).
2 GD group The level of serum CXCL10 in GD when they were patients onset、non-remission was significant higher than they were remission(p＜0.001) and controls(p＜0.001).There was no difference between patients onset and non-remission(p＞0.05).There was no difference between patients remission and controls(p＞0.05).The level of serum CXCL10 in 24 patients with GD before they therapied was significant higher than they were therapied by MMI after 3-6 months (p＜0.001).In GD group there was positive correlation between CXCL10 and FT3、FT4;there was no correlation between CXCL10 and TSH;there was no correlation in GD group between CXCL10 and TGAb、TMAb、TRAb,there was positive correlation between CXCL10 and TSI(p＜0.05).
3 HT group The level of serum CXCL10 in HT when they were patients onset was significant higher than they were remission and controls(p＜0.001).The level of serum CXCL10 in HT when they were patients non-remission was significant higher than they were remission and controls(p＜0.05).There was no difference between patients onset and non-remission(p＞0.05).There was no difference between patients remission and controls(p＞0.05).In HT group there was positive correlation between CXCL10 and sTSH(p＜0.01),there was no correlation between CXCL10 and FT3、FT4(p＞0.05);there was no correlation between CXCL10 and TGAb、TMAb、TRAb、TSI(p＞0.05).
Conclusion:
1 The level of serum chemokines CXCL10 in children AITD was higher than controls, so this study supporting that chemokines CXCL10 may participate in the immunoregulation of children AITD when they were invasion and development.
2 The circulating concentrations of CXCL10 have been found to be increased in GD and HT when they were initial stage and relapses,and they have been found to be decreased in AITD when they were remission.CXCL10 play an important role in the initial stage of children with AITD.,and there was close correlation between CXCL10 and the severity degree of disease.So CXCL10 may be as one of index to predict the reactiveness of disease.
引文
1 Rotondi M,Chiovato L,Romagnani S,et al.Role of Chemokines in Endocrine Autoimmune Diseases[J].Endocrine Reviews,2007,28(5):492-520.
2 Kemp EH,Metcalfe RA,Smith KA,et al.Detection and localization of chemokine gene expression in autoimmune thyroid disease[J].Clin Endocrinol,2003,59(2):207-213.
3 Romagnani P,Beltrame C,Annunziato F,et al.Role for interactions between IP-10/Mig and their receptor(CXCR3) in proliferative glomerulonephritis[J].Am Soc Nephrol,1999,10:2518-2526.
4 Garcia-Lopez MA,Sanchez-Madrid F,Rodrid F,Rodriguez-Frade JM,et al.CXCR3 chemokine receptor distribution in normal and inflamed tissues:expression on activated lymphocytes,endothelial cells,and dendritic cells[J].Lab Invest,2001,81:409-418.
5 Diez JJ,Hernanz A,Medina S,et al.Serum concentrations of tumour necrosis factor-α.(TNF-α) and soluble TNF-α.receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function[J].Clin Endocrinol,2002,57:515-521.
6 Antonelli A,Rotondi M,Fallahi P,et al.Iodine- 131 given for therapeutic purposes modulates differently interferon-gamma-inducible alpha-chemokine CXCL10serum levels in patients with active Graves' disease or toxic nodular goiter[J].Clin Endocrinol Metab.2007,92(4):1485-1490.
7 Antonelli A,Fallahi P,Rotondi M,et al.Serum levels of the interferon-gamma-inducible alpha chemokine CXCL10 in patients with active Graves' disease,and modulation by methimazole therapy and thyroidectomy[J].Surg.2006,93(10):1226-1231.
8 Antonelli A,Rotondi M,Fallahi P,et al.High Levels of Circulating CXC Chemokine Ligand 10 Are Associated with Chronic Autoimmune Thyroiditis and Hypothyroidism[J].Clin Endocrinol Metab,November,2004,89(11):5496-5499.
9 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-γ,inducible αchemokine CXCL10 but not β chemokine CCL2 serum levels in chronic autoimmune thyroiditis[J].European Journal of Endocrinology,2005,152 171-177.
10 齐翠娟,袁莉.趋化因子及其受体与自身免疫性甲状腺疾病[J].国际免疫学杂志,2007,30(3):181-184.
11.Bonecchi R,Bianchi G,Bordignon PP,et al.Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells(Th1s) and Th2s [J].Exp Med,1998,187:129-134.
12 Sallusto F,Lenig D,Mackay CR,et al.Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.[J]Exp Med,1998,187:875-883.
13 Romagnani P,Annunziato F,Lasagni L,et al.Cell cycle dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity[J].Clin Invest,2001,107:53-63.
14 Bonacchi A,Romagnani P,Romanelli RG,et al.Signal transduction by the chemokine receptor CXCR3:activation of Ras/ERK Src,and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes.[J]Biol Chem,2001,276:9945-9954.
15 Romagnani P,Beltrame C,Annunziato F,et al.Role for interactions between IP-10/Mig and their receptor(CXCR3) in proliferative glomerulonephritis.[J],Am Soc Nephrol,1999,10:2518-2526.
16 刘蓉,江昌新.IP-10和Mig及其受体与Graves病和桥本甲状腺炎[J]国际内分泌代谢杂志,2006,26(5):336-338.
17 Garcia-lopez MA,Sancho D,Sanchez-Madrid F,et al.Thyrocytes from autoimmune thyroid disorders produce the chemokines IP-10 and Mig and attract CXCR3~+lymphocytes[J].Clin Endocrinol Metal,2001,86;5008-5016.
18 SmitA 11,V erdijkP,va nd erR aaij-HehnerE M,et a 1.CX CR3-mediated chemotax is of human T cellsis regulatedaG i-a ndp hospholipaseC - dependent pathway and not activation of EM K/p44/p42M APKn orAk t/P I-3 kinase [J].Blood,2003,102:1959-1965.
19 ColvinR A,Ca mpanellaG S,Su nJ,et al.In tracellulard omainso fC XCR3 tha tm ed iate CXCL9,C XCL10,a nd CXCL11f unction[.J].B iolC hem,2004,279:30219-30227.
20 Weetman AP.autoimmune thyroid disease;propagation and progression[J].Eur J endocrinal,2003,148:1-9.
21 Diez JJ,Hernanz A,Medina S,et al.Serum concentrations of tumour necrosis factor-α.(TNF-α) and soluble TNF-α.receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function[J].Clin Endocrinol 2002 57:515-521
22 Salvi M,Pedrazzoni M,Girasole G,et al.Serum concentrations of proinflammatory cytokines in Graves' disease:effect of treatment,thyroid function,ophthalmopathy and cigarette smoking[J]Endocrinol 2000 143:197-202
23 Senturk T,Kozaci LD,Kok F,Proinflammatory cytokine levels in hyperthyroidism[J].Clin Invest Med 2003 26:58 -63
24 .Antonelli A,Fallahi P,Rotondi M,et al.Increase of interferon-y.inducible chemokine CXCL10 serum levels in patients with active Graves' disease,and modulation by methimazole therapy and thyroidectomy.[J]Surg 2006 93(10):1226-1231
25 Antonelli A,Rotondi M,Fallahi P,Iodine-131 given for therapeutic purposes modulates differently interferon-y.inducible .chemokine CXCL10 serum levels in patients with active Graves' disease or with toxic nodular goiter[J]Clin Endocrinol Metab 2007 92(4):1485-1490
26 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-y.inducible .chemokine CXCL10 but not P chemokine CCL2 serum levels in chronic autoimmune thyroiditis[J].Eur J Endocrinol 2005 152:171-177.
27 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-y inducible CXC chemokine CXCL10 serum Levels in patients with active Graves' disease,and modulation by methimazole therapy[J]Clin Endocrinol.(Oxf),2006,64:189-195.
28 Antonelli A,Fallahi P,Rotondi M,et al.Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper- or hypothyroidism per se,but is specifically sustained by the autoimmune,inflammatory process[J].European Journal of Endocrinology,2006 ,154:651-658.
29 Crescioli C,Cosmi L,Borgogni E,et al.Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes[J].Endocrinol.2007 ,195(1):145-155.
30.Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-yinducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease,and modulation by methimazole therapy[J]Clin Endocrinol 2006 64(2):189-195
31 Weetman A,Tandon N,Morgan B Anti-thyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells[J].Lancet 1992 340:633-636
32 Domberg J,Liu C,Papewalis C,et al.Circulating chemokines in patients with autoimmune thyroid diseases[J].Horm Metab Res.2008 ,40(6):416-421.
33 Corona G,Biagini C,Rotondi M,et al.Correlation between,clinical,biochemical,color Doppler ultrasound thyroid parameters,and CXCL-10 in autoimmunethyroid diseases[J].Endocr J.2008,55(2):345-350.
34 Mario Rotondi,Roberta Minellil,Flavia Magri,et al.Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-α therapy for hepatitis C virus-related hepatitis[J].European Journal of Endocrinology,2007,156 409-414.
35 Antonelli A,Rotondi M,Ferrari SM,et al.Interferon-y Inducible a Chemokine CXCL10 Involvement in Graves' Ophthalmopathy:Modulation by Peroxisome Proliferator-Activated Receptor-y Agonists[J]Clin Endocrinol Metab 2006, 91(2):614-620.
36 Proost P,Schutyser E,Menten P,et al.Ami nonterminal truncation of CXCR3 agonists impairs receptors signaling and lymphocyte chemotaxis,while preserving antiangiogenic properties[J].Blood,2001,98:3554-3561.
1 Zlotnik A,Yoshle O.A new classification system and their role in immunity.Immunity[J].2000,12:121-127.
2 Areberg DA,Polverini PJ,Kunkel SL,et al.The role of CXC chemokine in the regulation of angiogenesis in non-small cell lung cancer[J].Leukoc Biol 1997,62:554-562.
3 Muller A,Homey B,Soto H,et al.Involvement of chemokine receptors in breast cancer metastasis[J].Nature ,2001,410:50-56.
4 Yoshie OJmai T,Nomiyama H.Chemokines in immunity[J].Adv Immunol 2001,78:57-110.
5 Romagnani P,Lasagni L,Annunziato F,et al.CXC chemokines the regulatory link between inflammation and angiogenesis[J].Trends Immunol 2004,25:201-209.
6 .Bonecchi R,Bianchi G,Bordignon PP,et al.Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.[J]Exp Med 1998 187:129-134
7 Sallusto F,Lenig D,Mackay CR,et al.Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.[J]Exp Med 1998 187:875-883
8 Romagnani P,Annunziato F,Lasagni L,et al .Cell cycle dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity.[J]Clin Invest 2001 107:53-63
9 Bonacchi A,Romagnani P,Romanelli RG,et al.Signal transduction by the chemokine receptor CXCR3:activation of Ras/ERK Src,and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes.[J]Biol Chem 2001 276:9945-9954
10 Romagnani P,Beltrame C,Annunziato F,et al.Role for interactions between JP-10/Mig and their receptor (CXCR3) in proliferative glomerulonephritis.[J]Am Soc Nephrol 1999 10:2518-2526
11 Garcia-Lopez MA,Sanchez-Madrid F,Rodrid F,Rodriguez-Frade JM,et al.CXCR3 chemokine receptor distribution in normal and inflamed tissues:expression on activated lymphocytes,endothelial cells,and dendritic cells[J].Lab Invest,2001,81:409-418.
12 Lasagni L,Francalanci M,Annuziato F,et al.An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10,Mig,I-TAC,and acts as functional receptor for platelet factor 4[J].Exp Med,2003,197:1537-1549.
13 Diez JJ,Tlemanz A,Medina S,et al.Serum concentrations of tumour necrosis factor-α.(TNF-α) and soluble TNF-α.receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function[J].Clin Endocrinol 2002 57:515-521
14 Salvi M,Pedrazzoni M,Girasole G,et al.Serum concentrations of proinflammatory cytokines in Graves' disease:effect of treatment,thyroid function,ophthalmopathy and cigarette smoking[J]Endocrinol 2000 143:197-202
15 Senturk T,Kozaci LD,Kok F,Proinflammatory cytokine levels in hyperthyroidism[J].Clin Invest Med 2003 26:58 -63
16 .Antonelli A,Fallahi P,Rotondi M,et al.Increase of interferon-y.inducible .chemokine CXCL10 serum levels in patients with active Graves”disease,and modulation by methimazole therapy and thyroidectomy.[J]Surg 2006 93(10):1226-1231
17 Antonelli A,Rotondi M,Fallahi P,Iodine-131 given for therapeutic purposes modulates differently interferon-y.inducible .chemokine CXCL10 serum levels in patients with active Graves' disease or with toxic nodular goiter[J]Clin Endocrinol Metab 2007 92(4):1485-1490
18 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-y.inducible .chemokine CXCL10 but not (3 chemokine CCL2 serum levels in chronic autoimmune thyroiditis[J].Eur J Endocrinol 2005 152:171-177.
19 Domberg J,Liu C,Papewalis C,et al.Circulating chemokines in patients with autoimmune thyroid diseases[J].Horm Metab Res.2008 40(6):416-421.
20 Corona G,Biagini C,Rotondi M,Correlation between,clinical,biochemical,color Doppler ultrasound thyroid parameters,and CXCL-10 in autoimmune thyroid diseases[J].Endocr J.2008 55(2):345-350.
21 Romagnani P,Rotondi M,Lazzeri E,et al.Expression of IP-10/CXCL10 and Mig/ CXC19 in the thyroid and increased serum levels of IP-10/CXCL10 in the serum of subjects with recent onset Graves' disease[J]Pathol 2002 161(1):195-206
22 Antonelli A,Fallahi P,Rotondi M,et al.Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper-or hypothyroidism per se,but is specifically sustained by the autoimmune,inflammatory process[J]Endocrinol 2006 154(5):651-658
23 Kemp EH,Metcalfe RA,Smith KA,et al.Detection and localization of chemokine gene expression in autoimmune thyroid disease[J].Clin Endocrinol 2003,59:207-213
24 Crescioli C,Cosmi L,Borgogni E,et al.Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes[J]Endocrinol.2007 195(1):145-155.
25.Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-yinducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease,and modulation by methimazole therapy[J]Clin Endocrinol 2006 64(2):189-195
26 Weetman A,Tandon N,Morgan B Anti-thyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells[J].Lancet 1992 340:633-636
27 Antonelli A,Rotondi M,Ferrari SM,et al.Interferon-y Inducible a Chemokine CXCLIO Involvement in Graves' Ophthalmopathy:Modulation by Peroxisome Proliferator-Activated Receptor-y Agonists[J]Clin Endocrinol Metab 2006,91(2):614-620.
2 Kemp EH,Metcalfe RA,Smith KA,et al.Detection and localization of chemokine gene expression in autoimmune thyroid disease[J].Clin Endocrinol,2003,59(2):207-213.
3 Romagnani P,Beltrame C,Annunziato F,et al.Role for interactions between IP-10/Mig and their receptor(CXCR3) in proliferative glomerulonephritis[J].Am Soc Nephrol,1999,10:2518-2526.
4 Garcia-Lopez MA,Sanchez-Madrid F,Rodrid F,Rodriguez-Frade JM,et al.CXCR3 chemokine receptor distribution in normal and inflamed tissues:expression on activated lymphocytes,endothelial cells,and dendritic cells[J].Lab Invest,2001,81:409-418.
5 Diez JJ,Hernanz A,Medina S,et al.Serum concentrations of tumour necrosis factor-α.(TNF-α) and soluble TNF-α.receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function[J].Clin Endocrinol,2002,57:515-521.
6 Antonelli A,Rotondi M,Fallahi P,et al.Iodine- 131 given for therapeutic purposes modulates differently interferon-gamma-inducible alpha-chemokine CXCL10serum levels in patients with active Graves' disease or toxic nodular goiter[J].Clin Endocrinol Metab.2007,92(4):1485-1490.
7 Antonelli A,Fallahi P,Rotondi M,et al.Serum levels of the interferon-gamma-inducible alpha chemokine CXCL10 in patients with active Graves' disease,and modulation by methimazole therapy and thyroidectomy[J].Surg.2006,93(10):1226-1231.
8 Antonelli A,Rotondi M,Fallahi P,et al.High Levels of Circulating CXC Chemokine Ligand 10 Are Associated with Chronic Autoimmune Thyroiditis and Hypothyroidism[J].Clin Endocrinol Metab,November,2004,89(11):5496-5499.
9 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-γ,inducible αchemokine CXCL10 but not β chemokine CCL2 serum levels in chronic autoimmune thyroiditis[J].European Journal of Endocrinology,2005,152 171-177.
10 齐翠娟,袁莉.趋化因子及其受体与自身免疫性甲状腺疾病[J].国际免疫学杂志,2007,30(3):181-184.
11.Bonecchi R,Bianchi G,Bordignon PP,et al.Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells(Th1s) and Th2s [J].Exp Med,1998,187:129-134.
12 Sallusto F,Lenig D,Mackay CR,et al.Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.[J]Exp Med,1998,187:875-883.
13 Romagnani P,Annunziato F,Lasagni L,et al.Cell cycle dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity[J].Clin Invest,2001,107:53-63.
14 Bonacchi A,Romagnani P,Romanelli RG,et al.Signal transduction by the chemokine receptor CXCR3:activation of Ras/ERK Src,and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes.[J]Biol Chem,2001,276:9945-9954.
15 Romagnani P,Beltrame C,Annunziato F,et al.Role for interactions between IP-10/Mig and their receptor(CXCR3) in proliferative glomerulonephritis.[J],Am Soc Nephrol,1999,10:2518-2526.
16 刘蓉,江昌新.IP-10和Mig及其受体与Graves病和桥本甲状腺炎[J]国际内分泌代谢杂志,2006,26(5):336-338.
17 Garcia-lopez MA,Sancho D,Sanchez-Madrid F,et al.Thyrocytes from autoimmune thyroid disorders produce the chemokines IP-10 and Mig and attract CXCR3~+lymphocytes[J].Clin Endocrinol Metal,2001,86;5008-5016.
18 SmitA 11,V erdijkP,va nd erR aaij-HehnerE M,et a 1.CX CR3-mediated chemotax is of human T cellsis regulatedaG i-a ndp hospholipaseC - dependent pathway and not activation of EM K/p44/p42M APKn orAk t/P I-3 kinase [J].Blood,2003,102:1959-1965.
19 ColvinR A,Ca mpanellaG S,Su nJ,et al.In tracellulard omainso fC XCR3 tha tm ed iate CXCL9,C XCL10,a nd CXCL11f unction[.J].B iolC hem,2004,279:30219-30227.
20 Weetman AP.autoimmune thyroid disease;propagation and progression[J].Eur J endocrinal,2003,148:1-9.
21 Diez JJ,Hernanz A,Medina S,et al.Serum concentrations of tumour necrosis factor-α.(TNF-α) and soluble TNF-α.receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function[J].Clin Endocrinol 2002 57:515-521
22 Salvi M,Pedrazzoni M,Girasole G,et al.Serum concentrations of proinflammatory cytokines in Graves' disease:effect of treatment,thyroid function,ophthalmopathy and cigarette smoking[J]Endocrinol 2000 143:197-202
23 Senturk T,Kozaci LD,Kok F,Proinflammatory cytokine levels in hyperthyroidism[J].Clin Invest Med 2003 26:58 -63
24 .Antonelli A,Fallahi P,Rotondi M,et al.Increase of interferon-y.inducible chemokine CXCL10 serum levels in patients with active Graves' disease,and modulation by methimazole therapy and thyroidectomy.[J]Surg 2006 93(10):1226-1231
25 Antonelli A,Rotondi M,Fallahi P,Iodine-131 given for therapeutic purposes modulates differently interferon-y.inducible .chemokine CXCL10 serum levels in patients with active Graves' disease or with toxic nodular goiter[J]Clin Endocrinol Metab 2007 92(4):1485-1490
26 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-y.inducible .chemokine CXCL10 but not P chemokine CCL2 serum levels in chronic autoimmune thyroiditis[J].Eur J Endocrinol 2005 152:171-177.
27 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-y inducible CXC chemokine CXCL10 serum Levels in patients with active Graves' disease,and modulation by methimazole therapy[J]Clin Endocrinol.(Oxf),2006,64:189-195.
28 Antonelli A,Fallahi P,Rotondi M,et al.Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper- or hypothyroidism per se,but is specifically sustained by the autoimmune,inflammatory process[J].European Journal of Endocrinology,2006 ,154:651-658.
29 Crescioli C,Cosmi L,Borgogni E,et al.Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes[J].Endocrinol.2007 ,195(1):145-155.
30.Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-yinducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease,and modulation by methimazole therapy[J]Clin Endocrinol 2006 64(2):189-195
31 Weetman A,Tandon N,Morgan B Anti-thyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells[J].Lancet 1992 340:633-636
32 Domberg J,Liu C,Papewalis C,et al.Circulating chemokines in patients with autoimmune thyroid diseases[J].Horm Metab Res.2008 ,40(6):416-421.
33 Corona G,Biagini C,Rotondi M,et al.Correlation between,clinical,biochemical,color Doppler ultrasound thyroid parameters,and CXCL-10 in autoimmunethyroid diseases[J].Endocr J.2008,55(2):345-350.
34 Mario Rotondi,Roberta Minellil,Flavia Magri,et al.Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-α therapy for hepatitis C virus-related hepatitis[J].European Journal of Endocrinology,2007,156 409-414.
35 Antonelli A,Rotondi M,Ferrari SM,et al.Interferon-y Inducible a Chemokine CXCL10 Involvement in Graves' Ophthalmopathy:Modulation by Peroxisome Proliferator-Activated Receptor-y Agonists[J]Clin Endocrinol Metab 2006, 91(2):614-620.
36 Proost P,Schutyser E,Menten P,et al.Ami nonterminal truncation of CXCR3 agonists impairs receptors signaling and lymphocyte chemotaxis,while preserving antiangiogenic properties[J].Blood,2001,98:3554-3561.
1 Zlotnik A,Yoshle O.A new classification system and their role in immunity.Immunity[J].2000,12:121-127.
2 Areberg DA,Polverini PJ,Kunkel SL,et al.The role of CXC chemokine in the regulation of angiogenesis in non-small cell lung cancer[J].Leukoc Biol 1997,62:554-562.
3 Muller A,Homey B,Soto H,et al.Involvement of chemokine receptors in breast cancer metastasis[J].Nature ,2001,410:50-56.
4 Yoshie OJmai T,Nomiyama H.Chemokines in immunity[J].Adv Immunol 2001,78:57-110.
5 Romagnani P,Lasagni L,Annunziato F,et al.CXC chemokines the regulatory link between inflammation and angiogenesis[J].Trends Immunol 2004,25:201-209.
6 .Bonecchi R,Bianchi G,Bordignon PP,et al.Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.[J]Exp Med 1998 187:129-134
7 Sallusto F,Lenig D,Mackay CR,et al.Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.[J]Exp Med 1998 187:875-883
8 Romagnani P,Annunziato F,Lasagni L,et al .Cell cycle dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity.[J]Clin Invest 2001 107:53-63
9 Bonacchi A,Romagnani P,Romanelli RG,et al.Signal transduction by the chemokine receptor CXCR3:activation of Ras/ERK Src,and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes.[J]Biol Chem 2001 276:9945-9954
10 Romagnani P,Beltrame C,Annunziato F,et al.Role for interactions between JP-10/Mig and their receptor (CXCR3) in proliferative glomerulonephritis.[J]Am Soc Nephrol 1999 10:2518-2526
11 Garcia-Lopez MA,Sanchez-Madrid F,Rodrid F,Rodriguez-Frade JM,et al.CXCR3 chemokine receptor distribution in normal and inflamed tissues:expression on activated lymphocytes,endothelial cells,and dendritic cells[J].Lab Invest,2001,81:409-418.
12 Lasagni L,Francalanci M,Annuziato F,et al.An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10,Mig,I-TAC,and acts as functional receptor for platelet factor 4[J].Exp Med,2003,197:1537-1549.
13 Diez JJ,Tlemanz A,Medina S,et al.Serum concentrations of tumour necrosis factor-α.(TNF-α) and soluble TNF-α.receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function[J].Clin Endocrinol 2002 57:515-521
14 Salvi M,Pedrazzoni M,Girasole G,et al.Serum concentrations of proinflammatory cytokines in Graves' disease:effect of treatment,thyroid function,ophthalmopathy and cigarette smoking[J]Endocrinol 2000 143:197-202
15 Senturk T,Kozaci LD,Kok F,Proinflammatory cytokine levels in hyperthyroidism[J].Clin Invest Med 2003 26:58 -63
16 .Antonelli A,Fallahi P,Rotondi M,et al.Increase of interferon-y.inducible .chemokine CXCL10 serum levels in patients with active Graves”disease,and modulation by methimazole therapy and thyroidectomy.[J]Surg 2006 93(10):1226-1231
17 Antonelli A,Rotondi M,Fallahi P,Iodine-131 given for therapeutic purposes modulates differently interferon-y.inducible .chemokine CXCL10 serum levels in patients with active Graves' disease or with toxic nodular goiter[J]Clin Endocrinol Metab 2007 92(4):1485-1490
18 Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-y.inducible .chemokine CXCL10 but not (3 chemokine CCL2 serum levels in chronic autoimmune thyroiditis[J].Eur J Endocrinol 2005 152:171-177.
19 Domberg J,Liu C,Papewalis C,et al.Circulating chemokines in patients with autoimmune thyroid diseases[J].Horm Metab Res.2008 40(6):416-421.
20 Corona G,Biagini C,Rotondi M,Correlation between,clinical,biochemical,color Doppler ultrasound thyroid parameters,and CXCL-10 in autoimmune thyroid diseases[J].Endocr J.2008 55(2):345-350.
21 Romagnani P,Rotondi M,Lazzeri E,et al.Expression of IP-10/CXCL10 and Mig/ CXC19 in the thyroid and increased serum levels of IP-10/CXCL10 in the serum of subjects with recent onset Graves' disease[J]Pathol 2002 161(1):195-206
22 Antonelli A,Fallahi P,Rotondi M,et al.Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper-or hypothyroidism per se,but is specifically sustained by the autoimmune,inflammatory process[J]Endocrinol 2006 154(5):651-658
23 Kemp EH,Metcalfe RA,Smith KA,et al.Detection and localization of chemokine gene expression in autoimmune thyroid disease[J].Clin Endocrinol 2003,59:207-213
24 Crescioli C,Cosmi L,Borgogni E,et al.Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes[J]Endocrinol.2007 195(1):145-155.
25.Antonelli A,Rotondi M,Fallahi P,et al.Increase of interferon-yinducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease,and modulation by methimazole therapy[J]Clin Endocrinol 2006 64(2):189-195
26 Weetman A,Tandon N,Morgan B Anti-thyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells[J].Lancet 1992 340:633-636
27 Antonelli A,Rotondi M,Ferrari SM,et al.Interferon-y Inducible a Chemokine CXCLIO Involvement in Graves' Ophthalmopathy:Modulation by Peroxisome Proliferator-Activated Receptor-y Agonists[J]Clin Endocrinol Metab 2006,91(2):614-620.