Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways
Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways
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DOI：
10.1016/j.cellimm.2006.08.006
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发表时间：
2006-07-01
影响因子：
4.3
通讯作者：
Mansfield, John M.
中科院分区：
文献类型：
--
作者：
Curran, Colleen S.;Demick, Karen P.;Mansfield, John M.
乳铁蛋白 (LF) 是先天免疫的一个组成部分，已知与 TLR4 途径中涉及的辅助分子相互作用，包括 CD14 和 LPS 结合蛋白，表明 LF 可能激活 TLR4 途径的组成部分。在本研究中，我们询问牛 LF (bLF) 诱导的巨噬细胞活化是否依赖于 TLR4。 bLF 和 LPS 均刺激 RAW 264.7 巨噬细胞和 BALB/cJ 腹膜渗出巨噬细胞中 IL-6 的产生和 CD40 的表达。然而，在同系 TLR4(-/-) C.C3-Tlr4(lps-d) 小鼠的巨噬细胞中，CD40 不表达，而 IL-6 分泌相对于野生型细胞增加。 bLF 或 LPS 刺激后，RAW 264.7 细胞和 BALB/cJ 巨噬细胞中的信号成分 NF-kappa B、p38、ERK 和 JNK 被激活，表明 TLR4 依赖性 bLF 激活途径利用了 LPS 激活所共有的信号成分。在 TLR4 缺陷型巨噬细胞中，bLF 诱导 NF-κ B、p38、ERK 和 JNK 激活，而 LPS 诱导的细胞信号传导不存在。我们从这些研究中得出结论，bLF 通过 TLR4 依赖和独立机制诱导有限且明确的巨噬细胞激活和细胞信号传导事件。 bLF 诱导的 CD40 表达是 TLR4 依赖性的，而 bLF 诱导的 IL-6 分泌是 TLR4 独立的，表明先天免疫中 bLF 介导的巨噬细胞激活事件可能存在独立的途径。 (c) 2006 Elsevier Inc. 保留所有权利。
Lactoferrin (LF) is a component of innate immunity and is known to interact with accessory molecules involved in the TLR4 pathway, including CD14 and LPS binding protein, suggesting that LF may activate components of the TLR4 pathway. In the present study, we have asked whether bovine LF (bLF)-induced macrophage activation is TLR4-dependent. Both bLF and LPS stimulated IL-6 production and CD40 expression in RAW 264.7 macrophages and in BALB/cJ peritoneal exudate macrophages. However, in macrophages from congenic TLR4(-/-) C.C3-Tlr4(lps-d) mice, CD40 was not expressed while IL-6 secretion was increased relative to wild-type cells. The signaling components NF-kappa B, p38, ERK and JNK were activated in RAW 264.7 cells and BALB/cJ macrophages after bLF or LPS stimulation, demonstrating that the TLR4-dependent bLF activation pathway utilizes signaling components common to LPS activation. In TLR4 deficient macrophages, bLF-induced activation of NF-kappa B, p38, ERK and JNK whereas LPS-induced cell signaling was absent. We conclude from these studies that bLF induces limited and defined macrophage activation and cell signaling events via TLR4-dependent and -independent mechanisms. bLF-induced CD40 expression was TLR4-dependent whereas bLF-induced IL-6 secretion was TLR4-independent, indicating potentially separate pathways for bLF mediated macrophage activation events in innate immunity. (c) 2006 Elsevier Inc. All rights reserved.