PMID- 25068657
OWN - NLM
STAT- MEDLINE
DCOM- 20141230
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 94
IP  - 11
DP  - 2014 Nov
TI  - Lactoferrin suppresses the Epstein-Barr virus-induced inflammatory response by 
      interfering with pattern recognition of TLR2 and TLR9.
PG  - 1188-99
LID - 10.1038/labinvest.2014.105 [doi]
AB  - 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-kappaB activity. LF 
      interacted with TLR2 and interfered with EBV-triggered TLR2-NF-kappaB 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.
FAU - Zheng, Ying
AU  - Zheng Y
AD  - 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.
FAU - Qin, Zailong
AU  - Qin Z
AD  - 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.
FAU - Ye, Qiurong
AU  - Ye Q
AD  - 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.
FAU - Chen, Pan
AU  - Chen P
AD  - 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.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Diabetes Center, Second Xiangya Hospital, Institute of Metabolism and 
      Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, 
      Central South University, Changsha, China.
FAU - Yan, Qun
AU  - Yan Q
AD  - Department of Clinical Laboratory, Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Luo, Zhaohui
AU  - Luo Z
AD  - 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.
FAU - Liu, Xiaoping
AU  - Liu X
AD  - 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.
FAU - Zhou, Yanhong
AU  - Zhou Y
AD  - 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.
FAU - Xiong, Wei
AU  - Xiong W
AD  - 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.
FAU - Ma, Jian
AU  - Ma J
AD  - 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.
FAU - Li, Guiyuan
AU  - Li G
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140728
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 9)
RN  - EC 3.4.21.- (Lactoferrin)
SB  - IM
MH  - Chemokine CCL2/metabolism
MH  - Epstein-Barr Virus Infections/immunology
MH  - Female
MH  - HEK293 Cells
MH  - Herpesvirus 4, Human/*immunology
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Lactoferrin/*physiology
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Macrophages/*physiology
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/metabolism
MH  - Toll-Like Receptor 2/*immunology
MH  - Toll-Like Receptor 9/*immunology
MH  - Up-Regulation
EDAT- 2014/07/30 06:00
MHDA- 2014/12/31 06:00
CRDT- 2014/07/29 06:00
PHST- 2014/02/03 00:00 [received]
PHST- 2014/06/17 00:00 [revised]
PHST- 2014/06/30 00:00 [accepted]
PHST- 2014/07/29 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2014/12/31 06:00 [medline]
AID - S0023-6837(22)00769-3 [pii]
AID - 10.1038/labinvest.2014.105 [doi]
PST - ppublish
SO  - Lab Invest. 2014 Nov;94(11):1188-99. doi: 10.1038/labinvest.2014.105. Epub 2014 
      Jul 28.