Adhesion to fibronectin regulates interleukin-1 beta expression in microglial cells.
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.
Summers
Lauren
L
Faculty of Life Sciences, A.V Hill Building, University of Manchester, Oxford Road, Manchester M139PT, UK.
Kielty
Cay
C
Pinteaux
Emmanuel
E
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
D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D053583:Interleukin-1beta; D007797:Laminin; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines