A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R.
A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R.
复制标题
DOI：
10.1084/jem.188.7.1343
复制
发表时间：
1998-10-05
期刊：
影响因子：
--
通讯作者：
Kollias G
中科院分区：
文献类型：
--
作者：
Douni E;Kollias G
尽管有压倒性的证据表明p75肿瘤坏死因子受体(p75TNF-R)的增加伴随着特定的人类炎症病理的发展，如脓毒症时的多器官衰竭、炎症性肝病、胰腺炎、呼吸窘迫综合征或艾滋病，但该受体在体内的功能仍不清楚。我们在这里表明，在与人类疾病相关的水平上，在转基因小鼠中产生人p75TNF-R会导致严重的炎症综合征，主要累及胰腺、肝脏、肾脏和肺，其特征是外周血单个核细胞中的NF-κB活性结构性增加。这一过程被证明独立于肿瘤坏死因子、淋巴毒素α或p55肿瘤坏死因子受体的存在而演变，尽管共表达人肿瘤坏死因子转基因加速了病理。这些结果确立了p75TNF-R的增加在炎症性疾病的发病机制中的独立作用，并暗示该受体直接参与了广泛的人类炎症病理。
Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.
登录
查看更多内容
影响因子：
15.9
作者：
Aderka, D;Sorkine, P;Klausner, J
通讯作者：
Klausner, J
影响因子：
4.8
作者：
BOLDIN, MP;METT, IL;WALLACH, D
通讯作者：
WALLACH, D
影响因子：
10.5
作者：
Cheng, GH;Baltimore, D
通讯作者：
Baltimore, D
影响因子：
13
作者：
Aderka, Dan
通讯作者：
Aderka, Dan
影响因子：
56.9
作者：
DETOGNI, P;GOELLNER, J;CHAPLIN, DD
通讯作者：
CHAPLIN, DD