The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function.
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.
Falsig
Jeppe
J
Institute of Neuropathology, University of Zürich, Schmelzbergstrasse 12, CH-8032 Zürich, Switzerland. jeppefalsig.pedersen@usz.ch
Pörzgen
Peter
P
Lund
Søren
S
Schrattenholz
André
A
Leist
Marcel
M
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
D018946:Chemokine CCL5; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D009573:Nitrites; D012333:RNA, Messenger