Analysis of gene expression profile triggered by signal peptide of eosinophil cationic protein

The signal peptide of eosinophil cationic protein (ECPsp) is known to play an important role in translocating ECP to extracellular space. However, we previously discovered that ECPsp has a novel function of inhibiting microbial growth and regulating the gene expression of tumor growth factor-alpha (TGF-α) and epidermal growth factor receptor (EGFR) in mammalian cells. In the present study, we first generated a DNA microarray dataset, which showed that ECPsp up-regulated inflammatory molecules including cytokines, chemokines, interferon-induced molecules, and Toll-like receptors. We then generated a function linkage network by integrating the microarray dataset with the KEGG pathway database, and discovered that STAT1, an important factor regulating cytokine expression and release, served as a hub to connect the pathways of cytokine stimulation (TGF-α and EGFR) and inflammatory responses. Furthermore, integrating the ECPsp interactome dataset with the functional linkage network elucidated that STAT1 served as a hub to connect 3 functional clusters, including cell proliferation and survival, protein translational regulation, and inflammatory responses. Our approach involving experimental and computational systems biology provided predicted pathways and potential regulation for further characterization of the novel function of ECPsp under inflammatory conditions.