title: Interleukin 18 activates MAPKs and STAT3 but not NF-κB in hippocampal HT-22 cells.
abstract: Interleukin (IL)-18 is a cytokine previously demonstrated to participate in neuroinflammatory processes. Since the components of the IL-18 receptor complex are expressed in neurons throughout the brain, IL-18 is also believed to directly influence neuronal function. Here we tested this hypothesis on mouse hippocampal neurons by measuring the effects of IL-18 on three pathways previously shown to be regulated by this cytokine in non-neuronal cells: the MAPK pathways, p38 and ERK1/2 MAPKs, STAT3 and NF-κB. Experiments were carried out in vitro using the immortalized hippocampal neuronal line HT-22 or in vivo following i.c.v. injection with recombinant mouse IL-18. We showed that IL-18 did not activate NF-κB in HT-22 cells whereas it induced a rapid (within 15min) activation of the MAPK pathways. Moreover, we demonstrated that IL-18 treatment enhanced P-STAT3 (Tyr705)/STAT3 ratio in the nucleus of HT-22 cells after 30-60min of exposure. A similar increase in P-STAT3 (Tyr705)/STAT3 ratio was observed in the whole hippocampus one hour after i.c.v. injection. These data demonstrate that IL-18 can act directly on neuronal cells affecting the STAT3 pathway; therefore, possibly regulating the expression of specific genes within the hippocampus. This effect may help to explain some of the IL-18-induced effects on synaptic plasticity and functionality within the hippocampal system.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: silvia.alboni@unimore.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alboni
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Montanari
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Benatti
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.affiliation: Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rigillo
authors.affiliation: Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Joan M C
authors.initials: JM
authors.lastname: Blom
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Brunello
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Bruno
authors.initials: B
authors.lastname: Conti
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Kings College London, London, UK.
authors.forename: M Carmine
authors.initials: MC
authors.lastname: Pariante
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Tascedda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D053724:Receptors, Interleukin-18 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D020382:Interleukin-18; D016328:NF-kappa B; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Brain; HT-22; Hippocampus; IL-18; IL-18Rα; IL-18Rβ; Isoforms; NF-κB; STAT-3; Signaling