title: Adhesion to fibronectin regulates interleukin-1 beta expression in microglial cells.
abstract: The extracellular matrix (ECM) of the central nervous system (CNS) is rapidly degraded following acute brain injury, leading to inflammation and neuronal death. Under these conditions, the pro-inflammatory cytokine interleukin-1beta (IL-1beta) is primarily produced by microglial cells and is a key mediator of neuroinflammation, but whether the ECM regulates microglial IL-1 synthesis after CNS injury remains unknown. This study aimed to investigate whether cell attachment to ECM molecules modulated IL-1beta production in activated microglia in vitro. We found adhesion to fibronectin, fibrillin-1 and laminin promoted microglial cell adhesion and spreading, potentiated by bacterial lipopolysaccharide (LPS) treatment. Adhesion to fibronectin (but not fibrillin-1 or laminin) regulated IL-1beta expression via a cell density-dependent mechanism, whereby fibronectin-induced cell proliferation resulted in less IL-1beta being produced. These data suggest an important regulatory mechanism of IL-1 production, associated with microglial migration and proliferation, driven by ECM degradation and/or synthesis in an injured brain.
authors.affiliation: Faculty of Life Sciences, A.V Hill Building, University of Manchester, Oxford Road, Manchester M139PT, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Summers
authors.forename: Cay
authors.initials: C
authors.lastname: Kielty
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D053583:Interleukin-1beta; D007797:Laminin; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines