γ-干扰素
| IFN-γ | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal structure of a biologically active single chain mutant of human interferon gamma | |||||||||
| 鉴定 | |||||||||
| 标志 | ? | ||||||||
| Pfam | PF00714（旧版） | ||||||||
| Pfam宗系 | CL0053（旧版） | ||||||||
| InterPro | IPR002069 | ||||||||
| SCOP | 1rfb / SUPFAM | ||||||||
| |||||||||
| 临床资料 | |
|---|---|
| 商品名 | Actimmune |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601152 |
| ATC码 | |
| 识别信息 | |
| |
| CAS号 | 82115-62-6  98059-61-1 |
| DrugBank | |
| ChemSpider | |
| ChEMBL | |
| 化学信息 | |
| 化学式 | C761H1206N214O225S6 |
| 摩尔质量 | 17145.6 g/mol |
干扰素-γ（Interferon gamma、Interferon-γ、IFNG、IFNγ）是水溶性二聚体的细胞因子[2]。是II型干扰素的唯一成员[3]曾被称为巨噬细胞活化因子。
结构
干扰素-γ的单体是由六个α螺旋组成一个核心[4]和在C端区延伸展开的片断序列。
生物活性
所有的细胞都可以产生干扰素-α和干扰素-β， 而干扰素-γ只由自然杀伤细胞（NK细胞）和活化的T细胞产生。I型干扰素对酸稳定，而干扰素-γ则遇酸变性。
干扰素-γ具有抗病毒、免疫调节及抗肿瘤特性[5]。干扰素-γ可以与干扰素伽玛受体(IFNGR)结合，进而调节JAK-STAT通路。干扰素-γ激活抗原提呈细胞，通过上调转录因子T-bet而促进I型辅助T细胞(Th1细胞)的分化。
干扰素-γ是I型辅助T细胞(Th1细胞)的标志性的细胞因子。II型辅助T细胞(Th2细胞)释放白细胞介素-4（IL-4）和白细胞介素-13（IL-13）。自然杀伤细胞和CD8+T细胞也产生干扰素-γ。干扰素-γ通过迅速降解RANK-RANKL信号通路的TRAF6而抑制破骨细胞形成。
治疗用途
干扰素可以用来治疗传染病，但也能促成自体免疫。在接受干扰素伽玛治疗的病人中，多达19%的病人会有自体免疫.
干扰素IFNγ用于猪生殖与呼吸道综合症PRRSV的治疗上，有试验发现干扰素IFNγ能活化先天免疫细胞，进而达到抑制病毒数量的效果。[6]
A型流感的治疗上，也有小鼠试验表现出当缺失干扰素后，流感感染小鼠死亡率大幅提升且体内病毒数量维持高浓度水平；相较之下，体内有干扰素存在的小鼠，流感病毒数量随着干扰素的生成而逐渐下降。[7]
参考文献
- ^ PDB 1FG9; Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE. Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure. September 2000, 8 (9): 927–36. PMID 10986460. doi:10.1016/S0969-2126(00)00184-2.
- ^ Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859-63.
- ^ Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. August 1982, 298 (5877): 859–63. PMID 6180322. doi:10.1038/298859a0.
- ^ Ealick SE, et al., Three-dimensional structure of recombinant human interferon-gamma. Science. 1991 May 3;252(5006):698-702.
- ^ Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004 Feb;75(2):163-89.
- ^ Bautista, E. M.; Molitor, T. W. IFNγ inhibits porcine reproductive and respiratory syndrome virus replication in macrophages. Archives of Virology. 1999-06, 144 (6): 1191–1200. ISSN 0304-8608. doi:10.1007/s007050050578.
- ^ Hoshino, Akinori; Takenaka, Hiroshi; Mizukoshi, Osamu; Imanishi, Jiro; Kishida, Tsunataro; Tovey, Michael G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.
延伸阅读
- Hall, Stephen K. A commotion in the blood: life, death, and the immune system. New York: Henry Holt. 1997. ISBN 0-8050-5841-9.
- Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting.. Cytokine Growth Factor Rev. 2002, 13 (2): 95–109. PMID 11900986. doi:10.1016/S1359-6101(01)00038-7.
- Chesler DA, Reiss CS. The role of IFN-gamma in immune responses to viral infections of the central nervous system.. Cytokine Growth Factor Rev. 2003, 13 (6): 441–54. PMID 12401479. doi:10.1016/S1359-6101(02)00044-8.
- Dessein A, Kouriba B, Eboumbou C, Dessein H, Argiro L, Marquet S, Elwali NE, Rodrigues V, Li Y, Doumbo O, Chevillard C. Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis.. Immunol. Rev. 2005, 201: 180–90. PMID 15361241. doi:10.1111/j.0105-2896.2004.00195.x.
- Joseph AM, Kumar M, Mitra D. Nef: "necessary and enforcing factor" in HIV infection.. Curr. HIV Res. 2005, 3 (1): 87–94. PMID 15638726. doi:10.2174/1570162052773013.
- Copeland KF. Modulation of HIV-1 transcription by cytokines and chemokines.. Mini reviews in medicinal chemistry. 2006, 5 (12): 1093–101. PMID 16375755. doi:10.2174/138955705774933383.
- Chiba H, Kojima T, Osanai M, Sawada N. The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease.. Sci. STKE. 2006, 2006 (316): pe1. PMID 16391178. doi:10.1126/stke.3162006pe1.
- Tellides G, Pober JS. Interferon-gamma axis in graft arteriosclerosis.. Circ. Res. 2007, 100 (5): 622–32. PMID 17363708. doi:10.1161/01.RES.0000258861.72279.29.