title: Cross talk between cytokine and hyperthermia-induced pathways: identification of different subsets of NF-κB-dependent genes regulated by TNFα and heat shock.
abstract: Heat shock inhibits NF-κB signaling, yet the knowledge about its influence on the regulation of NF-κB-dependent genes is limited. Using genomic approaches, i.e., expression microarrays and ChIP-Seq, we aimed to establish a global picture for heat shock-mediated impact on the expression of genes regulated by TNFα cytokine. We found that 193 genes changed expression in human U-2 osteosarcoma cells stimulated with cytokine (including 77 genes with the κB motif in the proximal promoters). A large overlap between sets of genes modulated by cytokine or by heat shock was revealed (86 genes were similarly affected by both stimuli). Binding sites for heat shock-induced HSF1 were detected in regulatory regions of 1/3 of these genes. Furthermore, pre-treatment with heat shock affected the expression of 2/3 of cytokine-modulated genes. In the largest subset of co-affected genes, heat shock suppressed the cytokine-mediated activation (antagonistic effect, 83 genes), which genes were associated with the canonical functions of NF-κB signaling. However, subsets of co-activated and co-repressed genes were also revealed. Importantly, pre-treatment with heat shock resulted in the suppression of NF-κB binding in the promoters of the cytokine-upregulated genes, either antagonized or co-activated by both stimuli. In conclusion, we confirmed that heat shock inhibited activation of genes involved in the classical cytokine-mediated functions of NF-κB. On the other hand, genes involved in transcription regulation were over-represented in the subset of genes upregulated by both stimuli. This suggests the replacement of NF-κB-mediated regulation by heat shock-mediated regulation in the latter subset of genes, which may contribute to the robust response of cells to both stress conditions.
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland.|Institute of Automatic Control, Silesian University of Technology, Akademicka 16, Gliwice, Poland.
authors.forename: Patryk
authors.initials: P
authors.lastname: Janus
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland.|Faculty of Automatic Control, Electronics and Computer Sciences, Silesian University of Technology, Akademicka 16, Gliwice, Poland.|Department of Clinical Science, University of Bergen, Postboks 7804, Bergen, Norway.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stokowy
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Sciences, Silesian University of Technology, Akademicka 16, Gliwice, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Jaksik
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szoltysek
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan, Poland.|Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 84, Poznan, Poland.
authors.forename: Luiza
authors.initials: L
authors.lastname: Handschuh
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Podkowinski
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland.
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Widlak
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Sciences, Silesian University of Technology, Akademicka 16, Gliwice, Poland.|Department of Statistics, Rice University, 6100 Main Street, Houston, TX, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Kimmel
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland. widlak@io.gliwice.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D005334:Fever / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D018869:Heat-Shock Response; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: ChIP-seq; HSF1; Heat shock; Microarrays; NF-κB; Transcription factor binding