title: Genomic and proteomic microglial profiling: pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation.
abstract: Microglia, a primary immune effector cell of the central nervous system (CNS) affects homeostatic, neuroprotective, regenerative and degenerative outcomes in health and disease. Despite these broad neuroimmune activities linked to specific environmental cues, a precise cellular genetic profile for microglia in the context of disease and repair has not been elucidated. To this end we used nucleic acid microarrays, proteomics, immunochemical and histochemical tests to profile microglia in neuroprotective immune responses. Optic and sciatic nerve (ON and SN) fragments were used to stimulate microglia in order to reflect immune consequences of nervous system injury. Lipopolysaccharide and latex beads-induced microglial activation served as positive controls. Cytosolic and secreted proteins were profiled by surface enhanced laser desorption ionization-time of flight (SELDI-TOF) ProteinChip, 1D and 2D difference gel electrophoresis. Proteins were identified by peptide sequencing with tandem mass spectrometry, ELISA and western blot tests. Temporal expression of pro-inflammatory cytokines, antioxidants, neurotrophins, and lysosomal enzyme expression provided, for the first time, a unique profile of secreted microglia proteins with neuroregulatory functions. Most importantly, this molecular and biochemical signature supports a broad range of microglial functions for debris clearance and promotion of neural repair after injury.
authors: Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.
authors: Jason G
authors: JG
authors: Glanzer
authors: Yoshimi
authors: Y
authors: Enose
authors: Tong
authors: T
authors: Wang
authors: Irena
authors: I
authors: Kadiu
authors: Nan
authors: N
authors: Gong
authors: Wojciech
authors: W
authors: Rozek
authors: Jianuo
authors: J
authors: Liu
authors: Joshua D
authors: JD
authors: Schlautman
authors: Pawel S
authors: PS
authors: Ciborowski
authors: Mark P
authors: MP
authors: Thomas
authors: Howard E
authors: HE
authors: Gendelman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D020208:Brain Injury, Chronic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D020869:Gene Expression Profiling; D005911:Gliosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism; D009416:Nerve Regeneration / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D040901:Proteomics
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins