Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines.
Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines.
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DOI：
10.4049/jimmunol.0802971
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发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Ohashi PS
中科院分区：
文献类型：
--
作者：
Lu YC;Kim I;Lye E;Shen F;Suzuki N;Suzuki S;Gerondakis S;Akira S;Gaffen SL;Yeh WC;Ohashi PS
Toll样受体(TLR)的刺激通过MyD88和IRAK-4触发了一条信号通路，这是促炎细胞因子诱导所必需的。尽管核因子-κB已被证明是这些细胞因子的关键转录调节因子之一，但有证据表明，其他因素也可能是重要的。在这里，我们发现MyD88缺陷的巨噬细胞有缺陷的c-Rel激活，这与IL-12p40的诱导有关，但与IL-6或肿瘤坏死因子α无关。我们还研究了其他转录因子，发现在MyD88或IRAK-4缺陷的巨噬细胞中，C/EBPβ和C/EBPδ的表达受到限制。重要的是，C/EBPβ和C/EBPδ的缺失导致了由几种TLR配体刺激的促炎细胞因子的诱导受损。我们的结果确定c-Rel和C/EBPMyD88依赖的途径中的β/δ是重要的转录因子，调节促炎细胞因子的诱导。
Toll-like receptor (TLR) stimulation triggers a signaling pathway via MyD88 and IRAK-4 that is essential for proinflammatory cytokine induction. Although NF-κB has been shown to be one of the key transcriptional regulators of these cytokines, evidence suggests that other factors may also be important. Here we showed that MyD88-deficient macrophages have defective c-Rel activation, which has been linked to IL-12 p40 induction, but not IL-6 or TNFα. We also investigated other transcription factors and showed that C/EBPβ and C/EBPδ expression was limited in MyD88- or IRAK-4-deficient macrophages treated with LPS. Importantly, the absence of both C/EBPβ and C/EBPδ resulted in the impaired induction of proinflammatory cytokines stimulated by several TLR ligands. Our results identify c-Rel and C/EBPβ/δ as important transcription factors in a MyD88-dependent pathway that regulate the induction of proinflammatory cytokines.
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影响因子：
11.4
作者：
AKIRA, S;ISSHIKI, H;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
4.3
作者：
Boffa, DJ;Feng, B;Liou, HC
通讯作者：
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DOI：
10.1016/s0925-4439(00)00016-8
发表时间：
2000-06-15
影响因子：
6.2
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
10.5
作者：
DESCOMBES, P;CHOJKIER, M;SCHIBLER, U
通讯作者：
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