Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9
Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9
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DOI：
10.1038/labinvest.2014.105
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发表时间：
2014-07
影响因子：
5
通讯作者：
Ying Zheng;Zailong Qin;Q. Ye;Pan Chen;Zhen Wang;Qun Yan;Zhaohui Luo;Xiaoping Liu;Yanhong Zhou;W. Xiong;Jian Ma;Guiyuan Li
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文献类型：
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作者：
Ying Zheng;Zailong Qin;Q. Ye;Pan Chen;Zhen Wang;Qun Yan;Zhaohui Luo;Xiaoping Liu;Yanhong Zhou;W. Xiong;Jian Ma;Guiyuan Li
eb病毒（EBV）感染有助于多种人类恶性肿瘤的发生，包括鼻咽癌（NPC）。EBV部分通过toll样受体（TLR）信号传导触发先天免疫和炎症反应。乳铁蛋白（LF）具有抗炎特性，是先天免疫系统的重要组成部分。我们之前报道过，LF通过与EBV受体CD21结合的能力保护人类B淋巴细胞免受EBV感染，但LF是否能抑制EBV诱导的炎症尚不清楚。在这里，我们报道LF通过抑制NF-κB活性降低EBV诱导的巨噬细胞IL-8和单核细胞化学引诱蛋白-1 （MCP-1）的合成。LF与TLR2相互作用，干扰ebv触发的TLR2- nf -κB活化。LF通过结合其共受体CD14抑制TLR9识别dsDNA的能力，从而阻断CD14与TLR9的相互作用。因此，在CD14的存在下，ebv诱导的炎症会加重。此外，鼻咽癌标本中LF表达水平显著下调，且与IL-8和MCP-1表达呈负相关。这些发现表明，LF可能通过干扰TLR2和TLR9的激活来抑制ebv诱导的炎症反应。
Epstein–Barr virus (EBV) infection contributes to tumorigenesis of various human malignancies including nasopharyngeal carcinoma (NPC). EBV triggers innate immune and inflammatory responses partly through Toll-like receptor (TLR) signaling. Lactoferrin (LF), with its anti-inflammatory properties, is an important component of the innate immune system. We previously reported that LF protects human B lymphocytes from EBV infection by its ability to bind to the EBV receptor CD21, but whether LF can suppress EBV-induced inflammation is unclear. Here, we report that LF reduced synthesis of IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by EBV in macrophages via its suppression of NF-κB activity. LF interacted with TLR2 and interfered with EBV-triggered TLR2-NF-κB activation. LF inhibited the ability of TLR9 to recognize dsDNA by binding to its co-receptor CD14, which blocked the interaction between CD14 and TLR9. EBV-induced inflammation was thus aggravated in the presence of CD14. In addition, LF expression levels were significantly downregulated in NPC specimens, and correlated inversely with IL-8 and MCP-1 expression. These findings suggest that LF may suppress the EBV-induced inflammatory response through interfering with the activation of TLR2 and TLR9.