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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2010, Vol. 30 Issue (04): 95-100    
综述     
IFN-λs的最新研究进展
惠希武,陈虹,黄秉仁**
中国医学科学院基础医学研究所 北京协和医学院医学分子生物学国家重点实验室 北京 100005
The Latest Research Progress of IFN-λs
HUI Xi-wu,CHEN Hong,HUANG Bing-ren
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
 全文: PDF(895 KB)   HTML
摘要:

干扰素-λs(Interferon-λs, IFN-λs)是近年来发现的一类新型干扰素,由于其兼具I型干扰素和白细胞介素(interleukin, IL)-10家族的双重特征,因此其成员的命名为IFN-λ1(IL -29)、IFN-λ2(IL-28A)和IFN-λ3(IL-28B)。IFN-λs的受体隶属于II型细胞因子受体家族(class II cytokine receptor family, CRF2),由特有的配基结合亚基CRF2-12 /IFN-λR1 (又称IL-28Rα)和辅助亚基CRF2-4 (IL-10R2)组成。IFN-λs与I型IFN相同,均可通过激活JAK-STAT(janus kinase-signal transducer and activator of transcription)信号通路来传递配基结合信号,因此IFN-λs显示了与IFN-α相似的抗病毒、抑制肿瘤细胞生长以及具免疫调节功能等生物学活性,但由于其骨髓抑制及毒副作用少而生物学作用具长效性,且临床试验研究已经取得了突破性进展,故有望在不久的将来成为一个新的基因工程药物。

关键词: IFN-λsIFN-λ受体生物学功能    
Abstract:

 IFN-λs(including IFN-λ1, IFN-λ2, and IFN-λ3)is a newly identified IFN family whose characters related to the type I IFNs and IL-10 family members. IFNλs act through a cell surface receptor composed of two chains, the first one (CRF2-12/IFN-?R1/IL-28Rα) being IFN-λspecific and the second one (CRF2-4 / IL-10R2) shared with IL-10. IFN-λs signal through the IFN-λR1 and activate JAK-STATs pathways, as well as type I IFNs. So, IFN-λs exhibit several common features with type I IFNs: antiviral activity, antiproliferative activity and in vivo antitumour activity.And most importantly,clinical trialsⅠwith PEG-IFN-λ1was completed as a novel medcine to HCV. In this review, we summarize the lasted research progress about the biology of IFN-λs and point that IFN-λs may be applied to the clinical medicine in the near future.

Key words: IFN-λs    IFN-&lambda    receptor    Biological function
收稿日期: 2010-01-12 出版日期: 2010-04-29
基金资助:

国家自然科学基金资助项目(30470896)

通讯作者: 黄秉仁     E-mail: huangbr@public.bta.net.cn
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引用本文:

惠希武 陈虹 黄秉仁. IFN-λs的最新研究进展[J]. 中国生物工程杂志, 2010, 30(04): 95-100.

HUI Xi-Wu, CHEN Gong, HUANG Bing-Ren. The Latest Research Progress of IFN-λs. China Biotechnology, 2010, 30(04): 95-100.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2010/V30/I04/95

[1] Samarajiwa S A, Wilson W, Hertzog P J.Type I interferons: Genetics and structure, in: A. Meager The Interferons.Weinheim: WileyVCH,2006.334. 
[2] Kotenko SV, Gal1agber G, Baurin W, et al. IFNλs mediate antiviral protection through a distinct class II cytokine receptor complex. Nature Inmmnol, 2003, 4(1):6977. 
[3] Sheppard P, Kindsvogel W, Xu W, et al. IL28, IL29 and their class II cytokine receptor IL28R. Nature Immunol, 2003, 4(1):6368. 
[4] Lasfar A, LewisAntes, Kotenko S V, et al. Characterization of the mouse IFNlambda ligandreceptor system: IFNlambdas exhibit antitumor activity against B16 melanoma, Cancer Res,2006,66(8):44684477. 
[5] Chen Q, Carroll H P, Gadina M. The newest interleukins:recent additions to the evergrowing cytokine family. Vitam Horm, 2006,74:207228. 
[6] Dumoutier L, Renauld J C. Viral and cellular intedeukin10(IL10)related cytokines: from structures to functions. Eur Cytokine New, 2002,13(1):515. 
[7] Berghall H, Siren J, Sarkar D, et al. The interferoninducible RNA helicase is involved in measles virusinduced expression of antiviral cytokines. Microbes Infect, 2006,8(8):21382144. 
[8] Brand S, Beigel F, Olszak T, et al. IL28A and IL29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL28A expression. Am J Physiol Gastrointest Liver Physiol, 2005,289(5):960968. 
[9] Siren J, Pirhonen J, Julkunen I, et al. IFNα regulates TLRdependent gene expression of IFNα, IFNβ, IL28, and IL29. J. Immunol. 2005,174(4):19321937. 
[10] Coccia E M, Severa M, Giacomini E,et al. Viral infection and Tolllike receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocytederived dendritic cells. Eur J Immunol, 2004,34(3):796805. 
[11] Osterlund P, Veckman V, Siren J, et al. Gene expression and antiviral activity of α/β interferons and interleukin29 in virusinfected human myeloid dendriticcells. J Virol,2005,79(15):96089617. 
[12] Spann K M, Tran K C, Chi B, et al. Suppression of the induction of α, β, and λ interferons by the NS1 andNS2 proteins of human respiratory syncytial virus in human epithelialcells and macrophages. J Virol, 2004,78(8):43634369. 
[13] Kotenko S V. The family of ILl0related cytokines and their receptors: related, but to what extent? Cytokine Growth Factor Rev, 2002,13(3):223240. 
[14] Renanld J C. ClassⅡcytokine receptors and their ligands: key antiviral and inflammatory modulators. Nature Rev Immunol,2003, 3(8):667676. 
[15] Uze G, Monneron D. IL28 and IL29: Newcomers to the interferon family. Biochimie, 2007,89(67):729734. 
[16] Witte K, Gruetz G,Volk H D,et al.Despite IFNλ receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implica tions for therapeutic applications of these cytokines. Genes and Immun, 2009,10(8):702714. 
[17] Vilcek J. Novel interferons. Nature Imnmnol, 2003, 4(1): 89. 
[18] Dumoutier L, Tounsi A, Michiels T, et al. Role of interleukin IL28 receptor tyrosine residues for antival and antiproliferative activity of IFNλ1/interferonλ1. J Bio Chem, 2004, 279(31): 3226932274. 
[19] Dumoutier L, Lejeune D, Hor S, et al. Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. Biochem J, 2003, 370(pt2):391396. 
[20] Meager A, Visvalingam K, Diger P, et al. Biological activity of interleukins28 and29: Comparison with type I interferons. Cytokine, 2005, 31(2):109118. 
[21] Jordan WJ, Eskdale J, Srinivas S, et al. Human interferon lambda1 (IFNλ1) modulates the Th1/Th2 response,Genes and Immunity,2007,8(3):254261. 
[22] Robek M D, Boyd B S, Chisari F V. Lambda interferon inhibits hepatitis B and C virus replication. J Virol, 2005,79(6):38513854. 
[23] Andrew J M, Mitchell L, Shiffman M L, et al. Phase 1b doseranging study of 4 weeks of PEGInterferon (IFN) Lambda (PEGrIL29) in Combination with Ribavirin (RBV) in Patients with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection AASLD. The Liver Meeting in Boston, MA, October 30  November 3, 2009. 
[24] Li WA. Regulation of apoptosis by type III interferons. Cell Prolif, 2008,41(6):960979. 
[25] Numasaki M, Tagawa M, Iwata F, et al. IL28 elicits antitumor responses against murine fibrosarcoma. J Immunol, 2007,178(8):50865098. 
[26] Sato A,Ohtsuki M,Hata M, et al. Antitumor activity of IFNλ in murine tumor models the journal of immunology,2006, 176(12):76867694. 
[27] Mennechet F J, Uzé G. Interferonlambdatreated dendritic cells specifically induce proliferation of FOXP3expressing suppressor T cells. Blood, 2006, 107(11):44174423. 
[28] Maher S G, Sheikh F,Scarzello A J, et al. IFNα and IFNλ differ in their antiproliferative effects and uration of JAK/STAT signaling activity,Cancer Biol Ther, 2008,7(7):11091115. 
[29] Zitzmann K, Brand S, Baehs S, et al. Novel interferonλs induce antiproliferative effects in neuroendocrine tumor cells. Biochemical and Biophysical Research Communications, 2006,344(4):13341341. 
[30] Li Q, Kawamura K, Ma G, et al. Interferonλ induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces antitumour effects in combination with anticancer agents, Eur J Cancer, 2010,46(1):180190.

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