title: An anti-inflammatory role for C/EBPδ in human brain pericytes.
abstract: Neuroinflammation contributes to the pathogenesis of several neurological disorders and pericytes are implicated in brain inflammatory processes. Cellular inflammatory responses are orchestrated by transcription factors but information on transcriptional control in pericytes is lacking. Because the transcription factor CCAAT/enhancer binding protein delta (C/EBPδ) is induced in a number of inflammatory brain disorders, we sought to investigate its role in regulating pericyte immune responses. Our results reveal that C/EBPδ is induced in a concentration- and time-dependent fashion in human brain pericytes by interleukin-1β (IL-1β). To investigate the function of the induced C/EBPδ in pericytes we used siRNA to knockdown IL-1β-induced C/EBPδ expression. C/EBPδ knockdown enhanced IL-1β-induced production of intracellular adhesion molecule-1 (ICAM-1), interleukin-8, monocyte chemoattractant protein-1 (MCP-1) and IL-1β, whilst attenuating cyclooxygenase-2 and superoxide dismutase-2 gene expression. Altered ICAM-1 and MCP-1 protein expression were confirmed by cytometric bead array and immunocytochemistry. Our results show that knock-down of C/EBPδ expression in pericytes following immune stimulation increased chemokine and adhesion molecule expression, thus modifying the human brain pericyte inflammatory response. The induction of C/EBPδ following immune stimulation may act to limit infiltration of peripheral immune cells, thereby preventing further inflammatory responses in the brain.
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain Research.
authors.forename: Justin
authors.initials: J
authors.lastname: Rustenhoven
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain Research.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Scotter
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Gravida National Centre for Growth and Development [3] Centre for Brain Research.
authors.forename: Deidre
authors.initials: D
authors.lastname: Jansson
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain Research.
authors.forename: Dan T
authors.initials: DT
authors.lastname: Kho
authors.affiliation: The University of Auckland, 1023, Auckland, New Zealand.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Oldfield
authors.affiliation: 1] Centre for Brain Research [2] Lab Plus, Auckland City Hospital, 1023, Auckland, New Zealand.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Bergin
authors.affiliation: 1] Centre for Brain Research [2] Lab Plus, Auckland City Hospital, 1023, Auckland, New Zealand.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Mee
authors.affiliation: 1] Department of Anatomy with Radiology [2] Centre for Brain Research.
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.affiliation: 1] Department of Anatomy with Radiology [2] Centre for Brain Research.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Curtis
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain Research.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Graham
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain Research.
authors.forename: Thomas I-H
authors.initials: TI
authors.lastname: Park
authors.affiliation: 1] Department of Pharmacology and Clinical Pharmacology [2] Gravida National Centre for Growth and Development [3] Centre for Brain Research.
authors.forename: Mike
authors.initials: M
authors.lastname: Dragunow
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000893:Anti-Inflammatory Agents; D051743:CCAAT-Enhancer-Binding Protein-delta; D018799:Intercellular Adhesion Molecule-1; D053583:Interleukin-1beta; D016209:Interleukin-8; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C497252:CEBPD protein, human; C508606:CXCL8 protein, human