title: Lactoferrin suppresses the Epstein-Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9.
abstract: 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.
authors: 1] Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [2] Center for Medical Research, Second Xiangya Hospital, Central South University, Changsha, China.
authors: Ying
authors: Y
authors: Zheng
authors: Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors: Zailong
authors: Z
authors: Qin
authors: Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors: Qiurong
authors: Q
authors: Ye
authors: 1] Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [2] Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
authors: Pan
authors: P
authors: Chen
authors: Diabetes Center, Second Xiangya Hospital, Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, China.
authors: Zhen
authors: Z
authors: Wang
authors: Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China.
authors: Qun
authors: Q
authors: Yan
authors: Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors: Zhaohui
authors: Z
authors: Luo
authors: Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China.
authors: Xiaoping
authors: X
authors: Liu
authors: 1] Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [2] Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
authors: Yanhong
authors: Y
authors: Zhou
authors: 1] Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [2] Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
authors: Wei
authors: W
authors: Xiong
authors: 1] Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [2] Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
authors: Jian
authors: J
authors: Ma
authors: 1] Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China [2] Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
authors: Guiyuan
authors: G
authors: Li
mesh_terms: D018932:Chemokine CCL2 / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007781:Lactoferrin / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; C495342:TLR2 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D007781:Lactoferrin