IL-6 IS AN AUTOCRINE GROWTH FACTOR FOR EBV IMMORTALIZED B CELLS
IL-6 IS AN AUTOCRINE GROWTH FACTOR FOR EBV IMMORTALIZED B CELLS
批准号:
3811218
负责人:
G TOSATO
金额:
$0.0万
依托单位:
--
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
EB病毒(Epstein-Barr virus,EBV)是一种感染人类B细胞的永生疱疹病毒
淋巴细胞EB病毒的诱导和维持机制
在B细胞中的永生化状态目前是未知的。最近的证据,
然而,已经表明EBV永生化的B细胞产生生长因子
活性,然后使用它们来维持增殖。
因此,有人认为,自分泌回路的建立可能是
EBV使B细胞永生化的基本特征。一些
分子被认为是自分泌生长的原因
刺激EBV永生化B细胞,包括可溶性CD 23和
新鉴定的具有IL-1生物活性的多肽。在本研究中,
我们已经确定白细胞介素-6,IL-6,作为一种自分泌生长因子,
EBV感染的B细胞。所有检测的淋巴母细胞系(12号)均产生
在可变量(0.5-50 U/ml 72 hr)中测量的IL-6生物活性,
标准B 9测定。此外,IL-6可以从
35-S-标记的所有EBV-永生化细胞系的上清液,使用
人IL-6的异源抗血清。当IL-6部分纯化时,
淋巴母细胞样细胞系的培养上清液,并与其他细胞系分离,
生长因子活性也存在,它作为一种自分泌生长
因子的细胞产生它,这种活动被中和,
通过针对人IL-6的单克隆抗体以及多克隆抗体。因此我们
已经鉴定IL-6是EBV永生化B的自分泌生长因子
细胞
英文摘要
Epstein-Barr virus (EBV) is an immortalizing herpesvirus for human B
lymphocytes. The mechanisms responsible for EBV induction and maintenance
of an immortalized state in B cells are presently unknown. Recent evidence,
however, has suggested that EBV-immortalized B cells produce growth factor
activities in the supernatant and then use them to sustain proliferation.
Thus, it was suggested that the establishment of an autocrine loop might be
an essential feature of B cell immortalization by EBV. A number of
molecules have been proposed as being responsible for autocrine growth
stimulation in EBV-immortalized B cells, including soluble CD 23 and a
newly identified polypeptide with IL-1 bioactivity. In the present study,
we have identified Interleukin-6, IL-6, as an autocrine growth factor for
EBV-infected B cells. All lymphoblastoid cell lines tested (no 12) produced
IL-6 bioactivity in variable amounts (0.5-50 U/ml 72 hr), as measured in a
standard B9 assay. In addition, IL-6 could be immunoprecipitated from
35-S-labelled supernatants of all EBV-immortalized cell lines tested, using
a heteroantiserum to human IL-6. When IL6 was partially purified from the
culture supernatant of a lymphoblastoid cell line and separated from other
growth factor activities also present, it acted as an autocrine growth
factor for the cells producing it, and this activity was neutralized both
by a monoclonal as well as by a polyclonal antibody to human IL-6. Thus, we
have identified IL-6 as an autocrine growth factor for EBV-immortalized B
cells.
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