title: Direct immunomodulatory influence of IFN-β on human astrocytoma cells.
abstract: Astrocytes actively play a pivotal role in inflammatory disease intensity of central nervous system especially multiple sclerosis (MS). Although IFN-β is a selective therapy for MS but the role of IFN-β in stimulating the astrocytes to produce cytokines is not clearly revealed. Therefore, it is encouraging to assess the modulatory role of IFN-β on astrocytes of brain tissue. The aim of our study was to analyze the molecular mechanisms of recombinant IFN-β 1a directly affecting IL-10, iNOS, MMP-9 and TIMP-1 expression in central nervous system for the first time. In this way, in vitro procedures conducted by human astrocytoma A172 and 1321N1 cell lines as a model system. The total RNA from A172 and 1321N1 cells treated with IFN-β and LPS/IFN-γ/IFN-β and untreated cells were extracted and evaluated for IL-10, iNOS, MMP-9 and TIMP-1 expression by real-time RT-PCR. We found a significant dose-dependent increase in IL-10 gene expression in A172 and 1321N1 cells treated with IFN-β or LPS/IFN-γ/IFN-β. Moreover, a significant decrease was observed in iNOS expression suggesting a similar mechanism of action for both cells. Eventually there were no significant changes concerning the modulation of the MMP-9 and TIMP-1 in response to IFN-β treatment. In part, the immunomodulatory effect of IFN-β may be due to increase of IL-10 and suppression of iNOS expression in astrocytes of brain tissue.
authors.affiliation: Cellular & Molecular Research Center, Iran University of Medical Sciences , Tehran , Iran .
authors.forename: Monireh
authors.initials: M
authors.lastname: Mohsenzadegan
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Fayazi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Abdolmaleki
authors.forename: Masoomeh
authors.initials: M
authors.lastname: Bakhshayesh
authors.forename: Farhad
authors.initials: F
authors.lastname: Seif
authors.forename: Kazem
authors.initials: K
authors.lastname: Mousavizadeh
mesh_terms: D001254:Astrocytoma / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; D007155:Immunologic Factors; D016753:Interleukin-10; D016899:Interferon-beta; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Astrocytoma cells; IFN-β; IL-10; MMP-9; TIMP-1; iNOS