期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 44, 期 3, 页码 272-281出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2010.03.013
关键词
Inflammation; Extracellular matrix; CNS; Interleukin; Integrin; Astrocytes
资金
- Medical Research Council UK
- Biotechnology and Biological Sciences Research Council UK
- Medical Research Council [G9219675] Funding Source: researchfish
- MRC [G9219675] Funding Source: UKRI
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-1 beta-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-1 beta-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. (C) 2010 Elsevier Inc. All rights reserved.
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