title: Molecular mechanisms and Th1/Th2 pathways in corticosteroid regulation of cytokine production.
abstract: We focus on how the IL-1 system, T-helper1 (Th1) or Th2 cytokines and glucocorticoids, converge to give a unified physiological response. Glucocorticoids inhibit IL-1 and IL-1 receptor antagonist (IL-1ra) expression, Th1 cytokines stimulate both and Th2 cytokines stimulate IL-1ra and inhibit IL-1. Thus, during the Th1 response there is a window for IL-1 inflammatory activity, absent during the Th2 response. We also study the interactions among glucocorticoid and cytokine transcriptional activity. Glucocorticoids inhibit cytokine-induced transcription factors (NFkB, AP1) and cytokines enhance glucocorticoid receptor (GR) transcriptional activity, thus reciprocally fine tuning immunological control mechanisms.
authors.affiliation: Laboratorio de Fisiología y Biología Molecular, Departamento de Biología, FCEN, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, (1428), Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Kovalovsky
authors.forename: D
authors.initials: D
authors.lastname: Refojo
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
authors.forename: E
authors.initials: E
authors.lastname: Arzt
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D010913:Pituitary-Adrenal System / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology; D015398:Signal Transduction; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D005938:Glucocorticoids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins