title: Adhesion to the extracellular matrix is required for interleukin-1 beta actions leading to reactive phenotype in rat astrocytes.
abstract: 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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Summers
authors.forename: Korakoch
authors.initials: K
authors.lastname: Kangwantas
authors.forename: Loan
authors.initials: L
authors.lastname: Nguyen
authors.forename: Cay
authors.initials: C
authors.lastname: Kielty
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
mesh_terms: 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
chemical_list: 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
references.citation: Int J Biochem Cell Biol. 2004 Jun;36(6):1046-69
references.pmid: 15094120
references.citation: J Biol Chem. 2005 Aug 26;280(34):30526-37
references.pmid: 15980072
references.citation: J Neuropathol Exp Neurol. 2001 Oct;60(10):961-71
references.pmid: 11589427
references.citation: Exp Dermatol. 2004 Feb;13(2):70-7
references.pmid: 15009099
references.citation: Biochem Soc Trans. 2005 Nov;33(Pt 5):891-5
references.pmid: 16246005
references.citation: Spine (Phila Pa 1976). 2005 Feb 1;30(3):291-3
references.pmid: 15682009
references.citation: Nat Med. 2001 Mar;7(3):324-30
references.pmid: 11231631
references.citation: J Neurosci. 2004 Mar 17;24(11):2837-45
references.pmid: 15028778
references.citation: J Exp Med. 1986 Aug 1;164(2):594-604
references.pmid: 3487617
references.citation: J Neurotrauma. 2007 Jan;24(1):226-30
references.pmid: 17263686
references.citation: Br J Pharmacol. 2002 May;136(2):312-20
references.pmid: 12010781
references.citation: Mol Cell Neurosci. 2009 Jun;41(2):148-55
references.pmid: 19250967
references.citation: Philos Trans R Soc Lond B Biol Sci. 1996 Feb 29;351(1336):151-7
references.pmid: 8650261
references.citation: J Biol Chem. 2009 Mar 27;284(13):8797-811
references.pmid: 19147496
references.citation: Stroke. 2004 Apr;35(4):998-1004
references.pmid: 15001799
references.citation: Acta Neuropathol. 1990;80(4):355-61
references.pmid: 2239147
references.citation: Cell Mol Life Sci. 2004 Aug;61(16):2031-45
references.pmid: 15316653
references.citation: Circulation. 2003 Aug 19;108(7):876-81
references.pmid: 12874183
references.citation: J Biol Chem. 2005 Aug 5;280(31):28803-10
references.pmid: 15964831
references.citation: J Biol Chem. 2002 Jul 26;277(30):26927-33
references.pmid: 12011049
references.citation: An Acad Bras Cienc. 2002 Dec;74(4):683-90
references.pmid: 12563417