Effect of IFN-α on KC and LIX expression: Role of STAT1 and its effect on neutrophil recruitment to the spleen after lipopolysaccharide stimulation

被引:4
|
作者
Pan, Huayang [1 ]
Ma, Yong [1 ]
Wang, Dawei [1 ]
Wang, Jizhou [1 ]
Jiang, Hongchi [1 ]
Pan, Shangha [1 ]
Zhao, Baolei [1 ]
Wu, Yaohua [1 ]
Xu, Dongsheng [1 ]
Sun, Xueying [1 ,2 ]
Liu, Lianxin [1 ]
Xu, Zhilin [3 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 1, Dept Gen Surg, Key Lab Hepatosplen Surg, Harbin 150001, Peoples R China
[2] Univ Auckland, Dept Mol Med & Pathol, Fac Med & Hlth Sci, Auckland 1, New Zealand
[3] Harbin Med Univ, Affiliated Hosp 1, Dept Pediat Surg, Harbin 150001, Peoples R China
关键词
IFN-alpha; LPS; KC; LIX; Neutrophil; INTERFERON-ALPHA; TNF-ALPHA; DENDRITIC CELLS; CHEMOKINES; ACTIVATION; RESPONSES; EOSINOPHILS; MECHANISMS; PNEUMONIA; PATHWAYS;
D O I
10.1016/j.molimm.2013.04.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The spleen is a crucial lymphoid organ. It is involved in the recruitment of various immunocytes to their correct locations using specific chemokines, but little is known concerning the role of type-I interferon (IFN) in the regulation of chemokines. In this study, we first used protein microarrays to assess the expression of keratinocyte-derived chemokine (KC) and lipopolysaccharide-induced CXC chemokine (LIX) in murine spleens. Both expressions were smoothly enhanced by IFN-alpha pretreatment after LPS injection. Then, we focused on the A regulation of KC, LIX, and their target cells, neutrophils, using an IFN-alpha neutralizing antibody and fludarabine (specific signal transducers and activators of transcription 1 - STAT1 inhibitor). Next, LPS was found to attenuate the production of KC and LIX in spleen. Even the elevated production of chemokines caused by exogenous IFN-alpha was found to be attenuated by fludarabine pretreatment. We later determined that the marginal zone and red pulp are the main sites of KC and LIX production. Last, we determined that the number of neutrophils was slightly increased by IFN-alpha treatment and diminished by IFN-alpha neutralization or fiudarabine treatment. Further, the elevated neutrophils due to exogenous IFN-alpha were partially reversed by fludarabine pretreatment. In this way, these results indicate that IFN-alpha facilitates KC and LIX expression in mouse spleens after an LPS challenge. This effect was found to be mainly dependent upon the activation of STAT1, it may be involved in the recruitment of neutrophils to the spleen for the clearance of pathogens. (C) 2013 Elsevier Ltd. All rights reserved.
引用
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页码:12 / 22
页数:11
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