白细胞介素-10

白细胞介素-10
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1ILK、1INR、1J7V、1LK3、1Y6K、2ILK、2H24
識別號
别名	IL10；, CSIF, GVHDS, IL-10, IL10A, TGIF, interleukin 10
外部ID	OMIM：124092 MGI：96537 HomoloGene：478 GeneCards：IL10
相關疾病
	貝賽特氏症、溃疡性结肠炎
基因位置（人类）
染色体	1號染色體
终止	206,774,541 bp
基因位置（小鼠）
染色体	小鼠1号染色体
终止	130,952,711 bp
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• 血浆蛋白结合; • 生長因子活性; • 細胞因子活性; • interleukin-10 receptor binding; • protein dimerization activity;
細胞組分	• 細胞外區域; • 細胞外空間;
生物學過程	• negative regulation of chronic inflammatory response to antigenic stimulus; • positive regulation of MHC class II biosynthetic process; • 內皮細胞凋亡過程的負調控; • 造血作用; • negative regulation of interferon-gamma production; • regulation of sensory perception of pain; • positive regulation of B cell apoptotic process; • negative regulation of chemokine (C-C motif) ligand 5 production; • response to inactivity; • negative regulation of cytokine activity; • negative regulation of interleukin-1 production; • cellular response to hepatocyte growth factor stimulus; • cellular response to estradiol stimulus; • negative regulation of interleukin-6 production; • 老化; • positive regulation of DNA-binding transcription factor activity; • negative regulation of apoptotic process; • negative regulation of cytokine production involved in immune response; • response to glucocorticoid; • cytoplasmic sequestering of NF-kappaB; • negative regulation of interleukin-18 production; • negative regulation of MHC class II biosynthetic process; • response to activity; • response to organic substance; • response to carbon monoxide; • leukocyte chemotaxis; • type 2 immune response; • negative regulation of myeloid dendritic cell activation; • response to insulin; • negative regulation of interleukin-8 production; • response to lipopolysaccharide; • B cell proliferation; • negative regulation of T cell proliferation; • negative regulation of nitric oxide biosynthetic process; • branching involved in labyrinthine layer morphogenesis; • defense response to bacterium; • regulation of complement-dependent cytotoxicity; • 免疫反应; • 基因調節; • B cell differentiation; • regulation of isotype switching; • 腫瘤壞死因子產生的負調控; • negative regulation of membrane protein ectodomain proteolysis; • inflammatory response; • cellular response to lipopolysaccharide; • negative regulation of B cell proliferation; • negative regulation of inflammatory response; • negative regulation of cytokine production; • positive regulation of transcription by RNA polymerase II; • negative regulation of interleukin-12 production; • defense response to protozoan; • negative regulation of sensory perception of pain; • positive regulation of macrophage activation; • liver regeneration; • regulation of synapse organization; • positive regulation of endothelial cell proliferation; • negative regulation of cell population proliferation; • negative regulation of heterotypic cell-cell adhesion; • positive regulation of heterotypic cell-cell adhesion; • positive regulation of cell cycle; • negative regulation of mitotic cell cycle; • endothelial cell apoptotic process; • regulation of response to wounding; • negative regulation of vascular associated smooth muscle cell proliferation; • positive regulation of vascular associated smooth muscle cell proliferation; • interleukin-12-mediated signaling pathway; • positive regulation of transcription, DNA-templated; • negative regulation of autophagy; • cytokine-mediated signaling pathway; • positive regulation of receptor signaling pathway via JAK-STAT; • positive regulation of pri-miRNA transcription by RNA polymerase II; • negative regulation of hydrogen peroxide-induced neuron death; • positive regulation of sprouting angiogenesis;
	Sources:Amigo / QuickGO
直系同源
	3586
	16153
	ENSG00000136634
	ENSMUSG00000016529
	P22301
	P18893
	NM_000572
	NM_010548
	NP_000563
	NP_034678
	維基數據
檢視/編輯人類	檢視/編輯小鼠

白细胞介素-10（亦稱為介白素-10，英文：Interleukin 10，簡稱IL-10），也称为细胞激素合成抑制因子（cytokine synthesis inhibitory factor，CSIF），是一种抗炎症细胞因子。在人类中，IL-10由「IL10」基因编码。^[6]IL-10的訊號需要藉由細胞膜上的介白素-10受體（IL-10受體）傳遞到細胞內。IL-10受體在作用時構型為含四個次單元的蛋白質複合體，其中包含兩個IL-10受體1（IL-10R1）單元以及兩個IL-10受體2（IL-10R2）單元。在接收到IL-10訊號時，IL-10R1會先直接與IL-10結合，之後呼叫（recruit）IL-10R2形成完整複合體，以進行後續的訊號傳遞，IL-10R2並不直接與IL-10結合。^[7]IL-10通过JAK1和Tyk2分别磷酸化IL-10受体1、IL-10受体2的胞质尾端，来诱导STAT3信号传递。

基因和蛋白质结构

IL-10蛋白是同型二聚体，每个亚基的长度均为178个氨基酸。^[8]

IL-10被归为2类细胞因子——包括IL-19、IL-20、IL-22、IL-24(Mda-7)、IL-26和I型干扰素（IFN-α,-β,-ε,-κ,-ω），II型（IFN-γ），III型（IFN-λ，^[9]也称为IL-28A，IL-28B，和IL-29）。^[10]

表达与合成

在人类中，IL-10由「IL10」基因编码，该基因位于1号染色体上，包含5个外显子^[6]，主要由单核细胞产生，并在较小程度上由淋巴细胞产生，即II型T辅助细胞（T_H2），肥大细胞，CD4⁺CD25⁺Foxp3⁺调节性T细胞，以及活化的T细胞和B细胞的某些子集。在这些细胞中触发PD-1后，单核细胞可以产生IL-10^[11]。IL-10上调也由GPCR介导，例如β-2肾上腺素^[12]和2型大麻素^[13]受体。IL-10的表达在未经刺激的组织中极少，似乎需要由共生或病原菌触发。^[14]IL-10表达在转录和转录后水平受到严格调节。刺激TLR或Fc受体途径后，在单核细胞中观察到广泛的IL-10基因座重塑^[15]。IL-10诱导涉及ERK1/2，p38和NF-κB信号传导，以及通过转录因子NF-κB和AP-1的启动子结合而引起的转录激活。IL-10可能通过负反馈回路自动调节其表达，该回路涉及IL-10受体的自分泌刺激和p38信号通路的抑制^[16]。此外，IL-10的表达在转录后水平受到广泛调控，这可能涉及通过富含AU的元件^[17]和诸如let-7^[18]或miR-106的microRNA控制mRNA的稳定性^[19]。

功能

IL-10是一种在免疫调节和炎症中具有多效性的细胞因子。它下调了巨噬细胞上Th1细胞因子、MHC-II类抗原、共刺激分子的表达。它还增强了B细胞的生存、增殖和产生抗体的能力。IL-10可以阻断NF-kB活动，并参与JAK-STAT信号转导通路的调节。

IL-10发现与1991年^[20]，最初报道其抑制细胞分泌、抗原呈递和CD4+细胞活化。^[21]^[22]^[23]^[24]进一步的研究表明，IL-10主要抑制脂多糖(LPS)和细菌产物介导的促炎性细胞因子TNFα^[25]、IL-1β^[25]、IL-12^[26]、IFNγ^[27]的分泌，这些细胞因子由Toll样受体（TLR）触发的骨髓细胞谱系分泌。

对肿瘤的影响

随着时间的流逝，IL-10功能的细微差别出现了，因为已证明对荷瘤小鼠的治疗可抑制肿瘤转移^[28]。多个实验室的进一步研究已经产生了进一步支持IL-10在免疫神经学背景下的免疫刺激能力的数据。从IL-10转基因小鼠^[29]中转染的肿瘤细胞系^[30]^[31]中表达IL-10或用IL-10给药可控制原发性肿瘤生长并降低转移负担。^[32]^[33]最近，聚乙二醇化重组鼠IL-10（PEG-rMuIL-10）已显示出诱导IFNγ和CD8⁺T细胞依赖性抗肿瘤免疫力^[34]^[35]。更具体地，已显示PEG化的重组人IL-10（PEG-rHuIL-10）增强细胞毒性分子粒酶B和穿孔素的CD8⁺T细胞分泌，并增强T细胞受体依赖性IFNγ的分泌^[36]。

在疾病中的作用

对小鼠的研究表明，肥大细胞也产生IL-10，抵消了这些细胞在变态反应部位的炎症作用^[37]。

IL-10能够抑制由巨噬细胞和Th1T细胞等细胞产生的促炎细胞因子如IFN-γ、IL-2、IL-3、TNFα和GM-CSF的合成。它也显示出抑制抗原呈递细胞的抗原呈递能力的强大能力。但是，它也对某些T细胞（Th2）和肥大细胞具有刺激性，并刺激B细胞成熟和抗体产生。

IL-10检查环氧合酶Cyclo-oxygenase-2（COX-2）的可诱导形式。缺乏IL-10已被证明可导致COX激活并导致血栓烷受体激活，从而引起小鼠血管内皮和心脏功能障碍。白介素10基因敲除脆弱的小鼠会随着年龄的增长而出现心脏和血管功能障碍^[38]。

IL-10与肌动蛋白有关，因为运动会引起IL-1ra，IL-10和sTNF-R的循环水平增加，这表明体育锻炼可促进抗炎细胞因子的形成。^[39]^[40]

与健康个体相比，在诊断为多发性硬化症的个体中观察到较低水平的IL-10^[41]。由于IL-10水平的降低，TNFα水平不能得到有效调节，因为IL-10可以调节TNF-α转化酶^[42]。结果，TNFα水平升高并导致炎症。^[43]TNFα本身通过TNF受体1诱导少突胶质细胞脱髓鞘，而慢性炎症与神经元脱髓鞘有关。

在黑素瘤细胞系中，IL-10调节NKG2D配体的表面表达。^[44]

临床使用或试验

在小鼠中进行的基因敲除研究表明，这种细胞因子在肠道中是必需的免疫调节剂。^[45]的确，克罗恩氏病患者对用重组白介素10产生细菌的治疗反应良好，证明了IL-10对抵消人体过度活跃的免疫反应的重要性。^[46]

根据数据，在临床试验中，数千名患有各种自身免疫性疾病的患者接受了重组人IL-10（rHuIL-10）的治疗。与预期相反，rHuIL-10治疗并未对克罗恩病患者的疾病产生重大影响。^[47]^[48]^[49]或类风湿关节炎。^[50]rHuIL-10治疗最初在牛皮癣中显示出有希望的临床数据。^[51]但在一项随机，双盲，安慰剂对照的II期临床试验中未能达到临床意义。^[52]对rHuIL-10在人类中作用的进一步研究表明，rHuIL-10除了抑制炎症外，还能够发挥促炎作用。^[53]^[54]

聚乙二醇化形式

除这些数据外，目前正在进行一项I期免疫科学临床试验，以评估PEG化重组人IL-10（PEG-rHuIL-10，AM0010）的治疗能力。^[55]与临床前免疫免疫学数据一致，研究者报告了实质性的抗肿瘤功效。相反于所报告的在体外和体内产生的IL-10的免疫抑制作用，^[22]^[23]^[24]^[56]^[57]治疗癌症患者的PEG-重组人白介-10引发的剂量滴定感应的免疫刺激细胞因子IFNγ，IL-18，IL-7，GM-CSF和IL-4的表达。此外，接受治疗的患者的外周CD8+T细胞表达活化标记，例如程序性死亡配體1（PD-L1）+，淋巴细胞活化基因3（LAG3）+和Fas配体（FasL）升高，血清TGFβ降低，其折叠倍数增加。这些发现与使用PEG-rMuIL-10的已发表的临床前免疫科学报告^[34]^[35]以及以前用rHuIL-10治疗人类的发现一致。^[53]^[54]这些数据表明，尽管IL-10可以在细菌产物刺激的髓样细胞中发挥免疫抑制作用，但对人的rHuIL-10/PEG-rHuIL-10治疗主要是免疫刺激。截至2018年^[update]AM0010（又名pegilodecakin）正在进行3期临床试验。^[58]

互动

已经证明IL-10与白介素10受体α亚基相互作用。^[59]^[60]^[61]^[62]^[63]

IL-10受体复合物也需要IL10R2链来启动信号传导。这种配体-受体的组合存在于鸟类和青蛙中，也可能存在于骨鱼类中。

参考资料

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^ Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology. December 2000, 119 (6): 1461–72. PMID 11113067. doi:10.1053/gast.2000.20196.
^ Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group. Gastroenterology. August 1997, 113 (2): 383–9. PMID 9247454. doi:10.1053/gast.1997.v113.pm9247454.
^ Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. The Journal of Rheumatology. April 2003, 30 (4): 648–51. PMID 12672180.
^ Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial. Archives of Dermatology. February 1999, 135 (2): 187–92. PMID 10052405. doi:10.1001/archderm.135.2.187.
^ Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10. Archives of Dermatology. October 2002, 138 (10): 1341–6. PMID 12374540. doi:10.1001/archderm.138.10.1341.
^ ^53.0 ^53.1 Proinflammatory effects of IL-10 during human endotoxemia. Journal of Immunology. September 2000, 165 (5): 2783–9. PMID 10946310. doi:10.4049/jimmunol.165.5.2783.
^ ^54.0 ^54.1 Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma. Gut. February 2002, 50 (2): 191–5. PMC 1773093 . PMID 11788558. doi:10.1136/gut.50.2.191.
^ Infante, Jeffrey R.; Naing, Aung; Papadopoulos, Kyriakos P.; Autio, Karen A.; Ott, Patrick Alexander; Wong, Deborah Jean Lee; Falchook, Gerald Steven; Patel, Manish R.; Pant, Shubham. A first-in-human dose escalation study of PEGylated recombinant human IL-10 (AM0010) in advanced solid tumors.. ASCO Meeting Abstracts. 2015-05-20, 33 (15_suppl): 3017 [2020-03-03]. （原始内容 (vanc)存档于2015-12-22）.
^ Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. Journal of Neuroimmunology. July 1995, 60 (1–2): 165–8. PMID 7642744. doi:10.1016/0165-5728(95)00066-b.
^ Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. Journal of Immunology. June 1998, 160 (12): 5936–44. PMID 9637507.
^ Early Data Supports Phase 3 Trial of Pegilodecakin as Possible Treatment for Advanced Pancreatic Cancer. [2020-03-03]. （原始内容存档于2021-12-02）.
^ A receptor for interleukin 10 is related to interferon receptors. Proceedings of the National Academy of Sciences of the United States of America. December 1993, 90 (23): 11267–71. PMC 47963 . PMID 8248239. doi:10.1073/pnas.90.23.11267.
^ Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity. July 2001, 15 (1): 35–46. PMID 11485736. doi:10.1016/S1074-7613(01)00169-8.
^ Characterization of recombinant extracellular domain of human interleukin-10 receptor. The Journal of Biological Chemistry. May 1995, 270 (21): 12906–11. PMID 7759550. doi:10.1074/jbc.270.21.12906.
^ Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1. Acta Crystallographica Section D. December 2001, 57 (Pt 12): 1908–11. PMID 11717514. doi:10.1107/S0907444901016249.
^ Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization. European Journal of Biochemistry. May 1999, 262 (1): 134–41. PMID 10231374. doi:10.1046/j.1432-1327.1999.00363.x.

进一步阅读

Bortesi L, Rossato M, Schuster F, Raven N, Stadlmann J, Avesani L, Falorni A, Bazzoni F, Bock R, Schillberg S, Pezzotti M. Viral and murine interleukin-10 are correctly processed and retain their biological activity when produced in tobacco. BMC Biotechnology. March 2009, 9 (1): 22. PMC 2667500 . PMID 19298643. doi:10.1186/1472-6750-9-22.
Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology. 2001, 19 (1): 683–765. PMID 11244051. doi:10.1146/annurev.immunol.19.1.683.
Girndt M. Humoral immune responses in uremia and the role of IL-10. Blood Purification. 2003, 20 (5): 485–8. PMID 12207099. doi:10.1159/000063553.
Beebe AM, Cua DJ, de Waal Malefyt R. The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine & Growth Factor Reviews. 2003, 13 (4–5): 403–12. PMID 12220553. doi:10.1016/S1359-6101(02)00025-4.
Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM. The dual role of IL-10. Trends in Immunology. January 2003, 24 (1): 36–43. PMID 12495723. doi:10.1016/S1471-4906(02)00009-1.
Roncarolo MG, Battaglia M, Gregori S. The role of interleukin 10 in the control of autoimmunity. Journal of Autoimmunity. June 2003, 20 (4): 269–72. PMID 12791310. doi:10.1016/S0896-8411(03)00047-7.
Groux H, Cottrez F. The complex role of interleukin-10 in autoimmunity. Journal of Autoimmunity. June 2003, 20 (4): 281–5. PMID 12791313. doi:10.1016/S0896-8411(03)00044-1.
Llorente L, Richaud-Patin Y. The role of interleukin-10 in systemic lupus erythematosus. Journal of Autoimmunity. June 2003, 20 (4): 287–9. PMID 12791314. doi:10.1016/S0896-8411(03)00043-X.
Asadullah K, Sabat R, Friedrich M, Volk HD, Sterry W. Interleukin-10: an important immunoregulatory cytokine with major impact on psoriasis. Current Drug Targets. Inflammation and Allergy. June 2004, 3 (2): 185–92. PMID 15180472. doi:10.2174/1568010043343886.
Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimbürger O, Cederholm T, Girndt M. IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly. Kidney International. April 2005, 67 (4): 1216–33. PMID 15780075. doi:10.1111/j.1523-1755.2005.00200.x.
Chang CF, Wan J, Li Q, Renfroe SC, Heller NM, Wang J. Alternative activation-skewed microglia/macrophages promote hematoma resolution in experimental intracerebral hemorrhage. Neurobiol. Dis. July 2017, 103: 54–69. PMC 5540140 . PMID 28365213. doi:10.1016/j.nbd.2017.03.016.
Copeland KF. Modulation of HIV-1 transcription by cytokines and chemokines. Mini Reviews in Medicinal Chemistry. December 2005, 5 (12): 1093–101. PMID 16375755. doi:10.2174/138955705774933383.

外部链接

维基共享资源上的相關多媒體資源：白细胞介素-10
醫學主題詞表（MeSH）：Interleukin-10

[1] 與白细胞介素-10相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000136634 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000016529 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

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[pmid8590020-8] Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure. June 1995, 3 (6): 591–601. PMID 8590020. doi:10.1016/S0969-2126(01)00193-9.

[pmid26200010-9] Interferon-λ: Immune Functions at Barrier Surfaces and Beyond. Immunity. July 2015, 43 (1): 15–28. PMC 4527169 . PMID 26200010. doi:10.1016/j.immuni.2015.07.001.

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[pmid20208540-11] Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nature Medicine. April 2010, 16 (4): 452–9. PMC 4229134 . PMID 20208540. doi:10.1038/nm.2106.

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[13] Saroz, Yurii; Kho, Dan T.; Glass, Michelle; Graham, Euan Scott; Grimsey, Natasha Lillia. Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes. ACS Pharmacology & Translational Science. 2019-10-19, 2 (6): 414–428. ISSN 2575-9108. doi:10.1021/acsptsci.9b00049 （英语）.

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[pmid16184516-16] Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. European Journal of Immunology. October 2005, 35 (10): 2991–3001. PMID 16184516. doi:10.1002/eji.200526192.

[pmid10861064-17] Posttranscriptional regulation of IL-10 gene expression through sequences in the 3'-untranslated region. Journal of Immunology. July 2000, 165 (1): 292–6. PMID 10861064. doi:10.4049/jimmunol.165.1.292.

[pmid21468030-18] Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family. The EMBO Journal. May 2011, 30 (10): 1977–89. PMC 3098495 . PMID 21468030. doi:10.1038/emboj.2011.94.

[pmid19307576-19] Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a. Proceedings of the National Academy of Sciences of the United States of America. April 2009, 106 (14): 5761–6. PMC 2659714 . PMID 19307576. doi:10.1073/pnas.0808743106.

[20] Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology. 2001-01-01, 19 (1): 683–765. PMID 11244051. doi:10.1146/annurev.immunol.19.1.683.

[de_Waal_1991b-21] Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. The Journal of Experimental Medicine. November 1991, 174 (5): 1209–20. PMC 2119001 . PMID 1940799. doi:10.1084/jem.174.5.1209.

[de_Waal_1991-22] 22.0 ^22.1 Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. The Journal of Experimental Medicine. October 1991, 174 (4): 915–24. PMC 2118975 . PMID 1655948. doi:10.1084/jem.174.4.915.

[Akdis_2000-23] 23.0 ^23.1 A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. FASEB Journal. September 2000, 14 (12): 1666–8. PMID 10973911. doi:10.1096/fj.99-0874fje.

[Joss_2000-24] 24.0 ^24.1 IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. European Journal of Immunology. June 2000, 30 (6): 1683–90. PMID 10898505. doi:10.1002/1521-4141(200006)30:6<1683::AID-IMMU1683>3.0.CO;2-A.

[Opp_19952-25] 25.0 ^25.1 Opp MR, Smith EM, Hughes TK. Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. Journal of Neuroimmunology. July 1995, 60 (1–2): 165–8. PMID 7642744. doi:10.1016/0165-5728(95)00066-b.

[Aste-Amezaga_19982-26] Aste-Amezaga M, Ma X, Sartori A, Trinchieri G. Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. Journal of Immunology. June 1998, 160 (12): 5936–44. PMID 9637507.

[27] Varma TK, Toliver-Kinsky TE, Lin CY, Koutrouvelis AP, Nichols JE, Sherwood ER. Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice. Infection and Immunity. September 2001, 69 (9): 5249–63. PMC 98633 . PMID 11500393. doi:10.1128/iai.69.9.5249-5263.2001.

[28] Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. The Journal of Experimental Medicine. August 1996, 184 (2): 579–84. PMC 2192723 . PMID 8760811. doi:10.1084/jem.184.2.579.

[29] A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. Journal of Immunology. February 1999, 162 (3): 1723–9. PMID 9973435.

[30] Interleukin-10 gene transfer activates interferon-gamma and the interferon-gamma-inducible genes Gbp-1/Mag-1 and Mig-1 in mammary tumors. International Journal of Cancer. February 1999, 80 (4): 624–9. PMID 9935167. doi:10.1002/(sici)1097-0215(19990209)80:4<624::aid-ijc23>3.0.co;2-9.

[31] Essential role of nitric oxide and interferon-gamma for tumor immunotherapy with interleukin-10. Journal of Immunotherapy. 2000-04-01, 23 (2): 208–14. PMID 10746547. doi:10.1097/00002371-200003000-00005.

[32] Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood. October 2001, 98 (7): 2143–51. PMID 11568001. doi:10.1182/blood.v98.7.2143.

[33] Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice. Journal of Immunology. July 1996, 157 (1): 231–8. PMID 8683120.

[Emmerich_2012-34] 34.0 ^34.1 IL-10 directly activates and expands tumor-resident CD8(+) T cells without de novo infiltration from secondary lymphoid organs. Cancer Research. July 2012, 72 (14): 3570–81. PMID 22581824. doi:10.1158/0008-5472.CAN-12-0721.

[Mumm_2011-35] 35.0 ^35.1 IL-10 elicits IFNγ-dependent tumor immune surveillance. Cancer Cell. December 2011, 20 (6): 781–96. PMID 22172723. doi:10.1016/j.ccr.2011.11.003.

[36] The Potentiation of IFN-γ and Induction of Cytotoxic Proteins by Pegylated IL-10 in Human CD8 T Cells. Journal of Interferon & Cytokine Research. December 2015, 35 (12): 948–55. PMID 26309093. doi:10.1089/jir.2014.0221.

[pmid17767162-37] Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nature Immunology. October 2007, 8 (10): 1095–104. PMID 17767162. doi:10.1038/ni1503.

[pmid23159957-38] Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Experimental Gerontology. February 2013, 48 (2): 128–35. PMC 3744178 . PMID 23159957. doi:10.1016/j.exger.2012.11.001.

[pmid11192058-39] Physical activity and plasma interleukin-6 in humans--effect of intensity of exercise. European Journal of Applied Physiology. December 2000, 83 (6): 512–5. PMID 11192058. doi:10.1007/s004210000312.

[pmid9925898-40] Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. The Journal of Physiology. February 1999, 515 (1): 287–91. PMC 2269132 . PMID 9925898. doi:10.1111/j.1469-7793.1999.287ad.x.

[pmid10320650-41] Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment. Scandinavian Journal of Immunology. May 1999, 49 (5): 554–61. PMID 10320650. doi:10.1046/j.1365-3083.1999.00546.x.

[pmid18383040-42] Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism. European Journal of Immunology. April 2008, 38 (4): 1106–17. PMID 18383040. doi:10.1002/eji.200737821.

[Nakahara_2012-43] Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy. Clinical Reviews in Allergy & Immunology. February 2012, 42 (1): 26–34. PMID 22189514. doi:10.1007/s12016-011-8287-6.

[44] Interleukin 10 decreases MICA expression on melanoma cell surface. Immunology and Cell Biology. March 2011, 89 (3): 447–57. PMID 20714339. doi:10.1038/icb.2010.100.

[45] Entrez Gene: IL10 interleukin 10.

[pmid16716759-46] A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clinical Gastroenterology and Hepatology. June 2006, 4 (6): 754–9. PMID 16716759. doi:10.1016/j.cgh.2006.03.028.

[47] Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology. December 2000, 119 (6): 1473–82. PMID 11113068. doi:10.1053/gast.2000.20229.

[48] Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology. December 2000, 119 (6): 1461–72. PMID 11113067. doi:10.1053/gast.2000.20196.

[49] Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group. Gastroenterology. August 1997, 113 (2): 383–9. PMID 9247454. doi:10.1053/gast.1997.v113.pm9247454.

[50] Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. The Journal of Rheumatology. April 2003, 30 (4): 648–51. PMID 12672180.

[51] Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial. Archives of Dermatology. February 1999, 135 (2): 187–92. PMID 10052405. doi:10.1001/archderm.135.2.187.

[52] Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10. Archives of Dermatology. October 2002, 138 (10): 1341–6. PMID 12374540. doi:10.1001/archderm.138.10.1341.

[Lauw_2000-53] 53.0 ^53.1 Proinflammatory effects of IL-10 during human endotoxemia. Journal of Immunology. September 2000, 165 (5): 2783–9. PMID 10946310. doi:10.4049/jimmunol.165.5.2783.

[Tilg_2002-54] 54.0 ^54.1 Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma. Gut. February 2002, 50 (2): 191–5. PMC 1773093 . PMID 11788558. doi:10.1136/gut.50.2.191.

[Infante_2015-55] Infante, Jeffrey R.; Naing, Aung; Papadopoulos, Kyriakos P.; Autio, Karen A.; Ott, Patrick Alexander; Wong, Deborah Jean Lee; Falchook, Gerald Steven; Patel, Manish R.; Pant, Shubham. A first-in-human dose escalation study of PEGylated recombinant human IL-10 (AM0010) in advanced solid tumors.. ASCO Meeting Abstracts. 2015-05-20, 33 (15_suppl): 3017 [2020-03-03]. （原始内容 (vanc)存档于2015-12-22）.

[Opp_1995-56] Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. Journal of Neuroimmunology. July 1995, 60 (1–2): 165–8. PMID 7642744. doi:10.1016/0165-5728(95)00066-b.

[Aste-Amezaga_1998-57] Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. Journal of Immunology. June 1998, 160 (12): 5936–44. PMID 9637507.

[58] Early Data Supports Phase 3 Trial of Pegilodecakin as Possible Treatment for Advanced Pancreatic Cancer. [2020-03-03]. （原始内容存档于2021-12-02）.

[pmid8248239-59] A receptor for interleukin 10 is related to interferon receptors. Proceedings of the National Academy of Sciences of the United States of America. December 1993, 90 (23): 11267–71. PMC 47963 . PMID 8248239. doi:10.1073/pnas.90.23.11267.

[pmid11485736-60] Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity. July 2001, 15 (1): 35–46. PMID 11485736. doi:10.1016/S1074-7613(01)00169-8.

[pmid7759550-61] Characterization of recombinant extracellular domain of human interleukin-10 receptor. The Journal of Biological Chemistry. May 1995, 270 (21): 12906–11. PMID 7759550. doi:10.1074/jbc.270.21.12906.

[pmid11717514-62] Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1. Acta Crystallographica Section D. December 2001, 57 (Pt 12): 1908–11. PMID 11717514. doi:10.1107/S0907444901016249.

[pmid10231374-63] Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization. European Journal of Biochemistry. May 1999, 262 (1): 134–41. PMID 10231374. doi:10.1046/j.1432-1327.1999.00363.x.

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白细胞介素-10

基因和蛋白质结构

表达与合成

功能

对肿瘤的影响

在疾病中的作用

临床使用或试验

聚乙二醇化形式

互动

参考资料

进一步阅读

外部链接

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