Increased expression of the beta4 and alpha5 integrin subunits in cerebral blood vessels of transgenic mice chronically producing the pro-inflammatory cytokines IL-6 or IFN-alpha in the central nervous system.
Evidence suggests that vascular function is strongly regulated by extracellular matrix (ECM) proteins via integrin-mediated signaling. To determine whether integrin expression on cerebral blood vessels is altered during chronic neuroinflammation, we examined beta1 and beta4 integrin expression in transgenic mice with astrocyte production of the pro-inflammatory cytokines interleukin-6 (IL-6) or interferon-alpha (IFN-alpha). Chronic production of IL-6 or IFN-alpha in the CNS promoted vascular expression of the beta4 and alpha5 integrin subunits, and this was contributed mostly by astrocytes. Vascular expression of the ECM ligands laminin and fibronectin was also increased. Cell culture studies showed that astrocyte expression of the beta4 and alpha5 integrins was significantly upregulated by IL-6 and IFN-alpha, respectively, while endothelial expression of these integrins was unchanged. These results show that astrocytes respond to IL-6 and IFN-alpha by upregulating integrin expression. We propose that during neuroinflammation, astrocytes attempt to increase adhesive interactions at the blood-brain barrier (BBB), in order to increase barrier integrity.
Milner
Richard
R
Department of Molecular and Experimental Medicine, MEM-132, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. rmilner@scripps.edu
Campbell
Iain L
IL
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D039482:Integrin alpha5 / Q000378:metabolism*; D039663:Integrin beta4 / Q000378:metabolism*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic
D005904:Glial Fibrillary Acidic Protein; D039482:Integrin alpha5; D039663:Integrin beta4; D016898:Interferon-alpha; D015850:Interleukin-6