Chemoattraction of macrophages by secretory molecules derived from cells expressing the signal peptide of eosinophil cationic protein

doi:10.1186/1752-0509-6-105

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	Chemoattraction of macrophages by secretory molecules derived from cells expressing the signal peptide of eosinophil cationic protein
	Liu,Yu-Shu 1; Tsai,Pei-Wen 4; Wang,Yong5 ; Fan,Tan-chi 6; Hsieh,Chia-Hung 2; Chang,Margaret Dah-Tsyr 4,7; Pai,Tun-Wen 8; Huang,Chien-Fu 9; Lan,Chung-Yu 4; Chang,Hao-Teng 1,2,3
	2012-08-20
发表期刊	BMC Systems Biology
ISSN	1752-0509
卷号	6 期号:1
摘要	AbstractBackgroundEosinophil cationic protein is a clinical asthma biomarker that would be released into blood, especially gathered in bronchia. The signal peptide of eosinophil cationic protein (ECPsp) plays an important role in translocating ECP to the extracellular space. We previously reported that ECPsp inhibits microbial growth and regulates the expression of mammalian genes encoding tumor growth factor-α (TGF-α) and epidermal growth factor receptor (EGFR).ResultsIn the present study, we first generated a DNA microarray dataset, which showed that ECPsp upregulated proinflammatory molecules, including chemokines, interferon-induced molecules, and Toll-like receptors. The levels of mRNAs encoding CCL5, CXCL10, CXCL11, CXCL16, STAT1, and STAT2 were increased in the presence of ECPsp by 2.07-, 4.21-, 7.52-, 2.6-, 3.58-, and 1.67-fold, respectively. We then constructed a functional linkage network by integrating the microarray dataset with the pathway database of Kyoto Encyclopedia of Genes and Genomes (KEGG). Follow-up analysis revealed that STAT1 and STAT2, important transcriptional factors that regulate cytokine expression and release, served as hubs to connect the pathways of cytokine stimulation (TGF-α and EGFR pathways) and inflammatory responses. Furthermore, integrating TGF-α and EGFR with the functional linkage network indicated that STAT1 and STAT2 served as hubs that connect two functional clusters, including (1) cell proliferation and survival, and (2) inflammation. Finally, we found that conditioned medium in which cells that express ECPsp had been cultured could chemoattract macrophages. Experimentally, we also demonstrated that the migration of macrophage could be inhibited by the individual treatment of siRNAs of STAT1 or STAT2. Therefore, we hypothesize that ECPsp may function as a regulator for enhancing the migration of macrophages through the upregualtion of the transcriptional factors STAT1 and STAT2.ConclusionThe increased expression and release of various cytokines triggered by ECPsp may attract macrophages to bronchia to purge damaged cells. Our approach, involving experimental and computational systems biology, predicts pathways and potential biological functions for further characterization of this novel function of ECPsp under inflammatory conditions.
关键词	Eosinophil cationic protein (ECP) Signal peptide Inflammation Functional linkage network Cell migration
DOI	10.1186/1752-0509-6-105
语种	英语
WOS记录号	BMC:10.1186/1752-0509-6-105
出版者	BioMed Central
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/252
专题	应用数学研究所
通讯作者	Chang,Hao-Teng
作者单位	1.College of Medicine, China Medical University; Graduate Institute of Molecular Systems Biomedicine 2.College of Medicine, China Medical University; Graduate Institute of Basic Medical Science 3.China Medical University Hospital 4.National Tsing Hua University; Institute of Molecular and Cellular Biology 5.Chinese Academy of Sciences; Academy of Mathematics and Systems Science 6.Academia Sinica; Genomic Research Center 7.National Tsing Hua University; Department of Medical Science 8.National Taiwan Ocean University; Department of Computer Science and Engineering 9.I-Shou University; Department of Biological Science and Technology
推荐引用方式 GB/T 7714	Liu,Yu-Shu,Tsai,Pei-Wen,Wang,Yong,et al. Chemoattraction of macrophages by secretory molecules derived from cells expressing the signal peptide of eosinophil cationic protein[J]. BMC Systems Biology,2012,6(1).
APA	Liu,Yu-Shu.,Tsai,Pei-Wen.,Wang,Yong.,Fan,Tan-chi.,Hsieh,Chia-Hung.,...&Chang,Hao-Teng.(2012).Chemoattraction of macrophages by secretory molecules derived from cells expressing the signal peptide of eosinophil cationic protein.BMC Systems Biology,6(1).
MLA	Liu,Yu-Shu,et al."Chemoattraction of macrophages by secretory molecules derived from cells expressing the signal peptide of eosinophil cationic protein".BMC Systems Biology 6.1(2012).