title: The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function.
abstract: Upon injury, astrocytes assume an activated state associated with the release of inflammatory mediators. To model this, we stimulated murine primary astrocytes with a complete inflammatory cytokine mix consisting of TNF-alpha, IL-1beta and IFN-gamma. We analysed the transcriptional response of 480 genes at 4 and 16 h after stimulation on a chip designed to give a representative overview over the inflammation-relevant part of the transcriptome of macrophage-like cells. The list of the 182 genes found to be significantly regulated in astrocytes revealed an intriguing co-ordinate regulation of genes linked to the biological processes of antiviral/antimicrobial defence, antigen presentation and facilitation of leucocyte invasion. The latter group was characterized by very high up-regulations of chemokine genes. We also identified regulations of a thymidylate kinase and an interferon-regulated protein with a tetratricopeptide motive, both up to now only known from macrophages. The transcriptional regulations were confirmed on the protein level by a proteomic analysis. These findings taken together suggest that activated astrocytes in brain behave similarly in many respects to inflamed macrophages in the periphery.
authors.affiliation: Institute of Neuropathology, University of Zürich, Schmelzbergstrasse 12, CH-8032 Zürich, Switzerland. jeppefalsig.pedersen@usz.ch
authors.forename: Jeppe
authors.initials: J
authors.lastname: Falsig
authors.forename: Peter
authors.initials: P
authors.lastname: Pörzgen
authors.forename: Søren
authors.initials: S
authors.lastname: Lund
authors.forename: André
authors.initials: A
authors.lastname: Schrattenholz
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009573:Nitrites / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011247:Pregnancy; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013312:Stress, Physiological / Q000235:genetics; D013997:Time Factors
chemical_list: D018946:Chemokine CCL5; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D009573:Nitrites; D012333:RNA, Messenger