Send to

Choose Destination
See comment in PubMed Commons below
FASEB J. 2008 Mar;22(3):786-96. Epub 2007 Oct 26.

Glucocorticoids regulate innate immunity in a model of multiple sclerosis: reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells.

Author information

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.


Desensitization of seven transmembrane receptors (7TMRs), which are modulated by the beta-arrestins, leads to altered G protein activation. The A1 adenosine receptor (A1AR) is an antiinflammatory 7TMR exhibiting reduced expression and activity in both multiple sclerosis (MS) and the murine MS model, experimental autoimmune encephalomyelitis (EAE) in monocytoid cells. Herein, we report that beta-arrestin-1 expression was increased in brains of MS patients relative to non-MS brains, whereas A1AR expression was concomitantly reduced. This inverse relationship between beta-arrestin-1 and A1AR was confirmed in cultured monocytoid cells as beta-arrestin-1 overexpression resulted in a down-regulation of A1AR together with the internalization of the surface receptor. Moreover, a physical interaction between beta-arrestin-1 and A1AR was demonstrated in monocytoid cells. Proinflammatory cytokines regulated the A1AR/beta-arrestin-1 interactions, while A1AR activation also modulated proinflammatory cytokines expression. During EAE, beta-arrestin-1 and A1AR expression in the spinal cord displayed a similar pattern compared to that observed in MS brains. EAE-induced neuroinflammation and neurobehavioral deficits were suppressed by glucocorticoid treatments, accompanied by concurrent reduced beta-arrestin-1 and enhanced A1AR expression. Thus, the interplay between beta-arrestin-1 and A1AR in the central nervous system during neuroinflammation represents a reciprocal regulatory mechanism through which neuroprotective therapeutic strategies for neuroinflammatory diseases might be further developed.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center