title: Osteopontin directly modulates cytokine expression of primary microglia and increases their survival.
abstract: Osteopontin (OPN) is constitutively expressed in the brain and upregulated during neuroinflammation, e.g., focal cerebral ischemia. In OPN-deficient mice, microglia are deregulated after ischemia, but specific OPN-effects on microglia remain elusive. Primary microglia were cultured in the presence or absence of OPN. The survival of microglia under stress conditions was dose-dependently increased by OPN. Lipopolysaccharides (LPS)-induced release of nitric oxide (NO), TNF-α, and IL-6, as well as expression of inducible Nitric Oxide Synthase (iNOS), were attenuated by OPN. Data suggest that OPN modulates microglia function by shifting their inflammatory profile towards a neutral anti-inflammatory phenotype.
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Rabenstein
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sabine Ulrike
authors.initials: SU
authors.lastname: Vay
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lea Jessica
authors.initials: LJ
authors.lastname: Flitsch
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany.
authors.forename: Gereon Rudolf
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany. Electronic address: adele.rueger@uk-koeln.de.
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Rueger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D053495:Osteopontin / Q000494:pharmacology* / Q000502:physiology; D051381:Rats
chemical_list: D016207:Cytokines; C506897:Spp1 protein, rat; D053495:Osteopontin
keywords: Focal cerebral ischemia; Neural stem cells; Neuroinflammation; Neuroprotection; Regeneration