iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-κB-dependent blockade
iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-κB-dependent blockade
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DOI：
10.1002/eji.200838951
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发表时间：
2010-03-01
影响因子：
5.4
通讯作者：
Mevorach, Dror
中科院分区：
文献类型：
--
作者：
Amarilyo, Gil;Verbovetski, Inna;Mevorach, Dror
近年来，巨噬细胞和DC对凋亡细胞的清除不仅是非炎症性的，而且在大多数情况下（尽管不是所有情况）具有免疫抑制作用。在某些生理情况下，补体可能通过与桥接因子的直接结合，通过补体受体的调理和参与，参与凋亡细胞的摄取。在目前的研究中，我们使用了一种补体依赖系统，通过人源性巨噬细胞和DC清除凋亡细胞。利用荧光素酶报告基因并测量对非偶联酶的免疫反应，我们发现ic3b凋亡细胞在核易位、转录和转录后水平上诱导NF-kappa B抑制酶和LPS的反应，从而导致促炎细胞因子的深度抑制。此外，与ic3b -调理的凋亡细胞相互作用的特点是巨噬细胞分泌IL-10和缺乏tgf - β分泌。综上所述，在具有iC3b受体的细胞中，活化的凋亡细胞介导了明显的抗炎反应和转录nf - κ b依赖性阻断。
In recent years, it has become apparent that the removal of apoptotic cells by macrophages and DC is not only noninflammatory, but also immune-inhibitory, in most although not all circumstances. Complement may be involved in the uptake of apoptotic cells via direct binding of bridging factors in some physiological circumstances, by opsonization and engagement of the complement receptors. In the current study, we use a complement-dependent system of apoptotic cell clearance by human-derived macrophages and DC. Using a luciferase reporter gene and measuring immune response to non-opsonic zymosan, we show that iC3b-apoptotic cells induce NF-kappa B inhibition in response to zymosan and LPS at the nuclear translocation, transcriptional and post-transcriptional levels, leading to profound inhibition of proinflammatory cytokines. In addition, interaction with iC3b-opsonized apoptotic cells is characterized by macrophage secretion of IL-10 and lack of TGF-beta secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-kappa B-dependent blockage.