PMID- 19132682 OWN - NLM STAT- MEDLINE DCOM- 20090505 LR - 20220309 IS - 1615-9861 (Electronic) IS - 1615-9853 (Print) IS - 1615-9853 (Linking) VI - 9 IP - 3 DP - 2009 Feb TI - Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome. PG - 768-82 LID - 10.1002/pmic.200800385 [doi] AB - The roles of astrocytes in the CNS have been expanding beyond the long held view of providing passive, supportive functions. Recent evidence has identified roles in neuronal development, extracellular matrix maintenance, and response to inflammatory challenges. Therefore, insights into astrocyte secretion are critically important for understanding physiological responses and pathological mechanisms in CNS diseases. Primary astrocyte cultures were treated with inflammatory cytokines for either a short (1 day) or sustained (7 days) exposure. Increased interleukin-6 secretion, nitric oxide production, cyclooxygenase-2 activation, and nerve growth factor (NGF) secretion confirmed the astrocytic response to cytokine treatment. MS/MS analysis, computational prediction algorithms, and functional classification were used to compare the astrocyte protein secretome from control and cytokine-exposed cultures. In total, 169 secreted proteins were identified, including both classically and nonconventionally secreted proteins that comprised components of the extracellular matrix and enzymes involved in processing of glycoproteins and glycosaminoglycans. Twelve proteins were detected exclusively in the secretome from cytokine-treated astrocytes, including matrix metalloproteinase-3 (MMP-3) and members of the chemokine ligand family. This compilation of secreted proteins provides a framework for identifying factors that influence the biochemical environment of the nervous system, regulate development, construct extracellular matrices, and coordinate the nervous system response to inflammation. FAU - Keene, Sarah Dunn AU - Keene SD AD - Stokes Research Institute and Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA. FAU - Greco, Todd M AU - Greco TM FAU - Parastatidis, Ioannis AU - Parastatidis I FAU - Lee, Seon-Hwa AU - Lee SH FAU - Hughes, Ethan G AU - Hughes EG FAU - Balice-Gordon, Rita J AU - Balice-Gordon RJ FAU - Speicher, David W AU - Speicher DW FAU - Ischiropoulos, Harry AU - Ischiropoulos H LA - eng GR - AG13966/AG/NIA NIH HHS/United States GR - R01 AG013966-11/AG/NIA NIH HHS/United States GR - R21 MH084237/MH/NIMH NIH HHS/United States GR - R01 AG013966/AG/NIA NIH HHS/United States GR - P30 ES013508/ES/NIEHS NIH HHS/United States GR - ES013508/ES/NIEHS NIH HHS/United States GR - R21 MH084237-01A2/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - Germany TA - Proteomics JT - Proteomics JID - 101092707 RN - 0 (Cytokines) SB - IM MH - Animals MH - Astrocytes/*drug effects/*metabolism MH - Cells, Cultured MH - Cytokines/*pharmacology MH - Mice MH - Proteomics/methods MH - Tandem Mass Spectrometry/*methods PMC - PMC2667946 MID - NIHMS99991 EDAT- 2009/01/10 09:00 MHDA- 2009/05/06 09:00 PMCR- 2009/04/12 CRDT- 2009/01/10 09:00 PHST- 2009/01/10 09:00 [entrez] PHST- 2009/01/10 09:00 [pubmed] PHST- 2009/05/06 09:00 [medline] PHST- 2009/04/12 00:00 [pmc-release] AID - 10.1002/pmic.200800385 [doi] PST - ppublish SO - Proteomics. 2009 Feb;9(3):768-82. doi: 10.1002/pmic.200800385.