Paper Info
Title
Chemoattraction of macrophages by secretory molecules derived from cells expressing the signal peptide of eosinophil cationic protein.
Abstract
Eosinophil 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).In 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 upregulation of the transcriptional factors STAT1 and STAT2.The 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.
Year
DOI
Venue
2012
10.1186/1752-0509-6-105
BMC systems biology
Keywords
DocType
Volume
eosinophil cationic protein (ecp),cell migration,functional linkage network,signal peptide,inflammation,transforming growth factor alpha,chemokines,cluster analysis,eosinophil cationic protein,cell line,up regulation,systems biology,chemotactic factors,gene expression regulation,signal transduction
Journal
6
Issue
ISSN
Citations 
null
1752-0509
1
PageRank 
References 
Authors
0.34
2
10
Name
Order
Citations
PageRank
Yu-Shu Liu110.34
Pei-Wen Tsai221.38
Yong Wang357546.58
Tan-chi Fan4412.61
Chia-Hung Hsieh521.02
Margaret Dah-Tsyr Chang6888.87
Tun-Wen Pai712729.71
Chien-Fu Huang820.75
Chung-Yu Lan9232.29
Hao-Teng Chang1011511.04