Format

Send to

Choose Destination
Mol Neurobiol. 2019 Feb 23. doi: 10.1007/s12035-019-1527-0. [Epub ahead of print]

Delayed Galectin-3-Mediated Reprogramming of Microglia After Stroke is Protective.

Author information

1
CERVO Brain Research Centre, Université Laval, Québec, QC, G1J 2G3, Canada.
2
Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, 2601 Chemin de la Canardiere, Québec, QC, G1J 2G3, Canada.
3
Krembil Research Institute, University Health Network, Toronto, ON, Canada.
4
Glycobiology Laboratory, Research Centre for Infectious Disease, Université Laval, Quebec, QC, G1V 4G2, Canada.
5
CERVO Brain Research Centre, Université Laval, Québec, QC, G1J 2G3, Canada. jasna.kriz@fmed.ulaval.ca.
6
Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, 2601 Chemin de la Canardiere, Québec, QC, G1J 2G3, Canada. jasna.kriz@fmed.ulaval.ca.

Abstract

Galectin-3 (Gal-3), a β-galactoside-binding lectin, has recently emerged as a molecule with immunoregulatory functions. We investigated the effects of Gal-3 on microglia morphology, migration, and secretory profile under physiological conditions and in the context of ischemic injury. We show that in the control conditions, exposure to recombinant Gal-3 increases microglial ramification and motility in vitro and in vivo via an IL-4-dependent mechanism. Importantly, after stroke, Gal-3 exerted marked immune-modulatory properties. Delivery of Gal-3 at 24 h after middle cerebral artery occlusion (MCAO) was associated with an increase in Ym1-positive microglia and decrease in iNOS. Analysis of cytokine profiles at the protein level revealed downregulation of pro-inflammatory cytokines and a marked upregulation of the anti-inflammatory cytokine, IL-4, 24 h after i.c.v. injection of Gal-3. Importantly, the observed shift in cytokines in microglia was associated with a significant decrease in the infarct size. Taken together, our results suggest that when delivered well after ischemic injury, Gal-3 might fine tune innate immunity and induce a therapeutic shift in microglia polarization.

KEYWORDS:

Galectin-3; Innate immunity; Interleukin 4; Microglia; Stroke

PMID:
30798442
DOI:
10.1007/s12035-019-1527-0

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center