title: Integrating systemic information at the molecular level: cross-talk between steroid receptors and cytokine signaling on different target cells.
abstract: An essential event in immune activation is the increase of cytokines in both plasma and immune tissues. Steroid hormones influence several adaptive responses in both health and disease. Cytokines and steroids have an intimate cross-communication in many systems, making possible a satisfactory adaptive response to environmental changes. The ultimate level of integration of the cytokine-steroids cross-talk is the molecular level. We have demonstrated this in four types of cross-talk mechanisms on different cells in which steroids have major roles: (1) The tumor necrosis factor (TNF)-glucocorticoid receptor (GR) transcriptional interaction in cellular targets of TNF-induced cytotoxicity. TNF potentiates the transactivation activity of GR and the priming with TNF increases the protective action of GR on TNF-induced cytotoxicity. (2) The GR-T cell receptor (TCR) antagonism in GR-TCR-induced T cell apoptosis and its modulation by cAMP. cAMP inhibits the TCR-induced apoptosis through a PKA-CREB-dependent mechanism and potentiates glucocorticoid-induced apoptosis by means of a CREB-independent mechanism. (3) The GR influence on Th1-Th2 cytokine expression and differentiation. Glucocorticoids inhibit the induction of GATA-3 and T-bet transcription factors. (4) The influence of ER/Smad-4 signaling cross-communication on prolactinoma pathogenesis. Physical and functional interactions between Smad-4 and estrogen receptors take place in prolactinoma cells, providing a molecular explanation to link the tumorigenic action of these two important players of prolactinoma pathogenesis. The molecular cross-talk between steroids and transcription factors is the mechanism that provides the basis for the outcome of adaptive responses integrating the systemic information provided by hormones and cytokines.
authors.affiliation: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, and the Argentine National Research Council, Argentina.
authors.forename: Damián
authors.initials: D
authors.lastname: Refojo
authors.forename: Ana C
authors.initials: AC
authors.lastname: Liberman
authors.forename: Damiana
authors.initials: D
authors.lastname: Giacomini
authors.forename: Alberto
authors.initials: A
authors.lastname: Carbia Nagashima
authors.forename: Mariana
authors.initials: M
authors.lastname: Graciarena
authors.forename: Carlos
authors.initials: C
authors.lastname: Echenique
authors.forename: Marcelo
authors.initials: M
authors.lastname: Paez Pereda
authors.forename: Günter
authors.initials: G
authors.lastname: Stalla
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arzt
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology*; D006728:Hormones / Q000502:physiology; D006801:Humans; D010911:Pituitary Neoplasms / Q000276:immunology / Q000503:physiopathology; D015175:Prolactinoma / Q000276:immunology / Q000503:physiopathology; D020239:Receptor Cross-Talk / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013256:Steroids / Q000502:physiology
chemical_list: D016207:Cytokines; D006728:Hormones; D011987:Receptors, Steroid; D013256:Steroids