title: Emerging molecular networks common in ionizing radiation, immune and inflammatory responses by employing bioinformatics approaches.
abstract: Efficient radiation therapy is characterized by enhanced tumor cell killing involving the activation of the immune system (tumor immunogenicity) but at the same time minimizing chronic inflammation and radiation adverse effects in healthy tissue. The aim of this study was to identify gene products involved in immune and inflammatory responses upon exposure to ionizing radiation by using various bioinformatic tools. Ionizing radiation is known to elicit different effects at the level of cells and organism i.e. DNA Damage Response (DDR), DNA repair, apoptosis and, most importantly, systemic effects through the instigation of inflammatory 'danger' signals and innate immune response activation. Genes implicated both in radiation and immune/inflammatory responses were collected manually from the scientific literature with a combination of relevant keywords. The experimentally validated and literature-based results were inspected, and genes involved in radiation, immune and inflammatory response were pooled. This kind of analysis was performed for the first time, for both healthy and tumor tissues. In this way, a set of 24 genes common in all three different phenomena was identified. These genes were found to form a highly connected network. Useful conclusions are drawn regarding the potential application of these genes as markers of response to radiation for both healthy and tumor tissues through the modulation of immune and/or inflammatory mechanisms.
authors.affiliation: Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou 15780, Athens, Greece.
authors.forename: Alexandros G
authors.initials: AG
authors.lastname: Georgakilas
authors.affiliation: Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia 35100, Greece.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Pavlopoulou
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Zografou Campus, Athens 15701, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Louka
authors.affiliation: Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou 15780, Athens, Greece.
authors.forename: Zacharenia
authors.initials: Z
authors.lastname: Nikitaki
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Zografou Campus, Athens 15701, Greece.
authors.forename: Constantinos E
authors.initials: CE
authors.lastname: Vorgias
authors.affiliation: Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou, Athens 11527, Greece.
authors.forename: Pantelis G
authors.initials: PG
authors.lastname: Bagos
authors.affiliation: Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou, Athens 11527, Greece. Electronic address: imichalop@bioacademy.gr.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Michalopoulos
mesh_terms: D000818:Animals; D019295:Computational Biology; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007107:Immune System / Q000528:radiation effects*; D056747:Immunomodulation / Q000528:radiation effects; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000532:radiotherapy*
keywords: Bioinformatics; Biomarkers; Immune response; Inflammatory response; Ionizing radiation; Pathways