TY - JOUR
T1 - Adhesion to fibronectin regulates interleukin-1 beta expression in microglial cells
AU - Summers, Lauren
AU - Kielty, Cay
AU - Pinteaux, Emmanuel
PY - 2009/6/1
Y1 - 2009/6/1
N2 - 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-1β (IL-1β) 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-1β 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-1β expression via a cell density-dependent mechanism, whereby fibronectin-induced cell proliferation resulted in less IL-1β 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. © 2009 Elsevier Inc. All rights reserved.
AB - 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-1β (IL-1β) 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-1β 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-1β expression via a cell density-dependent mechanism, whereby fibronectin-induced cell proliferation resulted in less IL-1β 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. © 2009 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.mcn.2009.02.007
DO - 10.1016/j.mcn.2009.02.007
M3 - Article
C2 - 19250967
SN - 1095-9327
VL - 41
SP - 148
EP - 155
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 2
ER -