近期,国际病毒学顶级学术期刊《公共科学图书馆—病原体》( Plos Pathogens )发表了中国科学技术大学生命科学学院魏海明和田志刚教授研究组的科研成果——“TGF-b1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence”。揭示了乙型肝炎病毒逃避自然杀伤细胞的攻击,进而在人体长期存在的分子机制。文章第一作者是中国科学技术大学生命科学学院博士生孙成,通讯作者是魏海明和田志刚教授。 我国是乙型肝炎病毒感染大国,约有1.2亿人被乙肝病毒感染,母婴传播是乙肝病毒感染的主要途径,新生儿被感染后可在体内持续存在数年,在青春期后可陆续发病。迄今为止,尚不清楚乙肝病毒逃避机体免疫系统的攻击,并在体内长期生存的原因。 本研究对154例乙肝病毒携带者和乙肝病人进行系统免疫学研究,发现乙肝病毒持续感染者体内主要抗病毒免疫细胞—--自然杀伤细胞数量明显减少,残存的自然杀伤细胞也难以被激活,激发该细胞发挥杀伤病毒作用的双信号分子NKG2D/DAP10和2B4/SAP明显减弱,进一步分析原因发现,乙肝病毒携带者体内大量存在一种免疫抑制因子----转化生长因子b1(TGF-b1),该因子可导致自然杀伤细胞发生细胞周期阻滞,从而失去抗病毒作用,用抗转化生长因子b1抗体进行处理,可较大程度恢复自然杀伤细胞的功能。该研究对理解乙型肝炎病毒在人体内长期持续感染的机制有较大帮助。研究工作受国家基金委重点课题资助支持。(来源:中国科技大学) TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence The mechanism underlying persistent hepatitis B virus (HBV) infection remains unclear. We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls. The expression of NKG2D- and 2B4-activating receptors on NK cells was significantly decreased, and moreover, the expression of DAP10 and SAP, the intracellular adaptor proteins of NKG2D and 2B4 (respectively), were lower, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. Higher concentrations of transforming growth factor-beta 1 (TGF-β1) were found in sera from persistently infected HBV patients. TGF-β1 down-regulated the expression of NKG2D and 2B4 on NK cells in our in vitro study, leading to an impairment of their effector functions. Anti-TGF-β1 antibodies could restore the expression of NKG2D and 2B4 on NK cells in vitro. Furthermore, TGF-β1 induced cell-cycle arrest in NK cells by up-regulating the expression of p15 and p21 in NK cells from immunotolerant (IT) patients. We conclude that TGF-β1 may reduce the expression of NKG2D/DAP10 and 2B4/SAP, and those IT patients who are deficient in these double-activating signals have impaired NK cell function, which is correlated with persistent HBV infection. 作 者: Cheng Sun1, Binqing Fu1,2, Yufeng Gao3, Xiaofeng Liao1, Rui Sun1,2, Zhigang Tian1,2*, Haiming Wei1,2*
http://www.gopubmed.org/web/gopubmed/1?WEB05ajgv3ww6o3oI1yI1I00f01000j10040001rl 29 of 72 documents semantically analyzed Top Years Publications 2009 4 1998 3 1985 3 1971 3 2007 2 2005 2 1995 2 2008 1 2003 1 2002 1 1999 1 1996 1 1984 1 1983 1 1975 1 1973 1 1972 1 Top Countries Publications USA 6 Turkey 2 Japan 2 Greece 1 Taiwan 1 Germany 1 Croatia 1 Denmark 1 Top Cities Publications Wallingford 1 ?zmir 1 Athens 1 Houston 1 Taipei 1 Mibu 1 Bethesda 1 Pittsburgh 1 Leipzig 1 Ankara 1 Osijek 1 Cincinnati 1 Copenhagen 1 Seattle 1 1 2 Top Journals Publications World J Gastroentero 2 J Clin Oncol 2 Liver Int 1 Virchows Arch 1 J Formos Med Assoc 1 Alcohol 1 Cancer Immunol Immun 1 Mmw Fortschr Med 1 Jpn J Clin Oncol 1 Wien Med Wochenschr 1 Singapore Med J 1 Lik Sprava 1 J Hepatobiliary Pancreat Surg 1 Acta Oncol 1 Environ Health Persp 1 Adv Exp Med Biol 1 Klin Med (mosk) 1 Leber Magen Darm 1 Pol Tyg Lek 1 Hepato-gastroenterol 1 1 2 1 2 3 ... 6 Top Authors Publications Chen C 1 Iloeje U 1 Yang H 1 Jen C 1 Su J 1 Wang L 1 You S 1 Lu S 1 Kili M 1 Yaman B 1 Nart D 1 Yilmaz F 1 Coker A 1 Zeytunlu M 1 Vassilopoulos P 1 Korkolis D 1 Aggeli C 1 Plataniotis G 1 Gontikakis E 1 Zerbinis H 1 1 2 3 ... 6 1 2 3 ... 18 Top Terms Publications Pancreatic Neoplasms 29 Hepatitis B 29 Humans 28 Hepatitis 20 Middle Aged 16 Pancreatitis 14 Carcinoma 14 Liver Neoplasms 14 Patients 13 Viruses 12 Carcinoma, Hepatocellular 10 Neoplasms 10 Aged 10 Adult 9 Hepatitis Viruses 7 Diagnosis 7 Liver Cirrhosis 7 Pancreas 7 Pancrelipase 7 Hepatitis, Chronic 6 1 2 3 ... 18 http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi?refresh=TID=483 http://www.sciencenet.cn/htmlnews/2009/11/224784.shtm 研究显示感染乙肝病毒不会增加患胰腺癌风险 美国一项最新研究结果显示,感染乙肝病毒不会增加罹患胰腺癌的风险。 此前曾有研究显示,乙肝病毒感染与胰腺癌之间具有某种相关性。在1995年至2008年间,美国亨利福特医院研究人员对7.4万名乙肝病毒感染者的数据进行分析后推翻了这种观点。 研究报告主要撰稿人、亨利福特医院消化科医师杰弗里唐,在目前于波士顿召开的美国肝病研究学会年会上报告说,研究人员无法证实感染乙肝病毒会增加罹患胰腺癌的风险。他们认为,如果考虑年龄、种族、性别、糖尿病以及艾滋病病毒感染史等因素,年龄增长和糖尿病可能会增加患胰腺癌的风险。 胰腺癌是一种存活率很低的癌症。来自美国国家癌症研究所的数据显示,美国每年有超过33.5万人死于胰腺癌,另有4.2万个新确诊病例。 更多阅读 EurekAlert!相关报道(英文) http://www.eurekalert.org/pub_releases/2009-10/hfhs-hbd102909.php Hepatitis B does not increase risk for pancreatic cancer DETROIT A Henry Ford Hospital study found that hepatitis B does not increase the risk for pancreatic cancer and that only age is a contributing factor. The results contradict a previous study in 2008 that suggested a link between pancreatic cancer and previous hepatitis B infection. Hepatitis B is an inflammation of the liver caused by a viral infection. Study results will be presented at the American Association for the Study of Liver Diseases' Annual Meeting in Boston. Using data from Henry Ford Health System, physicians looked at more than 74,000 patients who were tested for hepatitis B between 1995 and 2008. In the overall analysis, only age was found to be a significant predictor for pancreatic cancer. We looked at the incidence of pancreatic cancer among hepatitis B-infected patients over a 13-year period and found that we could not confirm a higher risk for those with a previous exposure to hepatitis B, as a prior study suggested, says Jeffrey Tang, M.D., gastroenterologist at Henry Ford Hospital and lead author of the study. When other factors are considered such as age, race, sex, HIV status, and the presence of diabetes only older age and presence of diabetes proved significant, whereas prior exposure to hepatitis B was no longer an important variable. According to the National Cancer Institute, more than 35,000 people in the U.S. die of pancreatic cancer each year and 42,000 new cases are diagnosed. The survival rates for patients with pancreatic cancer are poor. An estimated 800,000 to 1.4 million people have chronic hepatitis B infection, according to the Centers for Disease Control and Prevention. In 2007, an estimated 43,000 people in the United States were newly infected with hepatitis B, although many cases are not reported because many people do not have symptoms. EDITOR'S NOTE: Dr. Jeffrey Tang is available for interviews. EMBARGOED FOR RELEASE 9 a.m., EST, Saturday, Oct. 31, 2009