Adhesion to the extracellular matrix is required for interleukin-1 beta actions leading to reactive phenotype in rat astrocytes.
The extracellular matrix (ECM) of the brain is essential for homeostasis and normal functions, but is rapidly remodelled during acute brain injury alongside the development of an inflammatory response driven by the cytokine interleukin (IL)-1. Whether the ECM regulates IL-1 actions in astrocytes is completely unknown. The aim of this study was to test the hypothesis that cellular attachment to the ECM is a critical mediator of IL-1beta-induced signalling pathways and development of reactive phenotype in astrocytes. Primary rat astrocytes adhered to fibronectin, laminin and fibrillin-1 in an integrin-dependent manner. Attachment to these ECM molecules significantly increased IL-1beta-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibition of RhoA and Rho kinase (ROCK), coincident with loss of focal adhesions and cellular morphological changes. Our data demonstrate that the ECM regulates IL-1 actions in astrocytes via cross-talk mechanisms between ERK1/2 and RhoA/ROCK, which could have important implications in brain inflammatory disorders.
Summers
Lauren
L
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Kangwantas
Korakoch
K
Nguyen
Loan
L
Kielty
Cay
C
Pinteaux
Emmanuel
E
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D004791:Enzyme Inhibitors; D019012:Integrin beta1; D053583:Interleukin-1beta; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D020742:rhoA GTP-Binding Protein
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