The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways
The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways
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DOI：
10.1016/s1074-7613(02)00423-5
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发表时间：
2002-10-01
期刊：
影响因子：
32.4
通讯作者：
Green, DR
中科院分区：
文献类型：
--
作者：
Dejardin, E;Droin, NM;Green, DR
淋巴毒素-β受体(LTbetaR)通过激活核因子-kappaB在炎症和淋巴器官形成中发挥重要作用。除了激活经典的核因子-kappaB外，该受体的连接还诱导胞浆中的核因子-kappaB2/P100前体的加工以产生成熟的p52亚基，随后p52转位到细胞核。NF-kappaB2的这种激活需要Nik和IKKalpha，而Nemo/IKKGamma对于P100的加工是必不可少的。在LTbetaR结扎反应中，P100的表达和包括VCAM-1、MIP-1β和MIP-2在内的促炎分子的表达都需要依赖于IKKβ的典型的NF-kappaB的激活，而不是处理。相比之下，IKKalpha控制LTbetaR连接对参与淋巴器官发生的趋化因子和细胞因子的诱导，包括SLC、BLC、ELC、SDF1和BAFF。
The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.