The authors have no conflict of interest in the publication of this manuscript.
Original Research Article
Transient acidification and subsequent proinflammatory cytokine stimulation of astrocytes induce distinct activation phenotypes†
Article first published online: 25 FEB 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 6, pages 1284–1294, June 2013
How to Cite
Renner, N. A., Sansing, H. A., Inglis, F. M., Mehra, S., Kaushal, D., Lackner, A. A. and MacLean, A. G. (2013), Transient acidification and subsequent proinflammatory cytokine stimulation of astrocytes induce distinct activation phenotypes. J. Cell. Physiol., 228: 1284–1294. doi: 10.1002/jcp.24283
- Issue published online: 25 FEB 2013
- Article first published online: 25 FEB 2013
- Accepted manuscript online: 14 NOV 2012 02:10PM EST
- Manuscript Accepted: 2 NOV 2012
- Manuscript Received: 23 MAR 2012
- PHS. Grant Numbers: OD11104, RR00164, MH077544
- AGM FMI. Grant Number: P20RR15637
- Tulane Committee on Research Summer Fellowship (AGM)
- Louisiana Board of Regents Fellowship LEQSF NAR. Grant Number: 2007–2012-GF15
The foot processes of astrocytes cover over 60% of the surface of brain microvascular endothelial cells, regulating tight junction integrity. Retraction of astrocyte foot processes has been postulated to be a key mechanism in pathology. Therefore, movement of an astrocyte in response to a proinflammatory cytokine or even limited retraction of processes would result in leaky junctions between endothelial cells. Astrocytes lie at the gateway to the CNS and are instrumental in controlling leukocyte entry. Cultured astrocytes typically have a polygonal morphology until stimulated. We hypothesized that cultured astrocytes which were induced to stellate would have an activated phenotype compared with polygonal cells. We investigated the activation of astrocytes derived from adult macaques to the cytokine TNF-α under resting and stellated conditions by four parameters: morphology, intermediate filament expression, adhesion, and cytokine secretion. Astrocytes were stellated following transient acidification; resulting in increased expression of GFAP and vimentin. Stellation was accompanied by decreased adhesion that could be recovered with proinflammatory cytokine treatment. Surprisingly, there was decreased secretion of proinflammatory cytokines by stellated astrocytes compared with polygonal cells. These results suggest that astrocytes are capable of multiple phenotypes depending on the stimulus and the order stimuli are applied. J. Cell. Physiol. 228: 1284–1294, 2013. © 2012 Wiley Periodicals, Inc.