Interferon beta-1a counteracts effects of activation on the expression of G-protein-coupled receptor kinases 2 and 3, beta-arrestin-1, and regulators of G-protein signalling 2 and 16 in human mononuclear leukocytes

Maurizio Giorelli; Paolo Livrea; Giovanni Defazio; Luisa Iacovelli; Loredana Capobianco; Antonietta Picascia; Michele Sallese; Davide Martino; Maria Stella Aniello; Maria Trojano; Antonio De Blasi

doi:10.1016/s0898-6568(02)00011-6

Interferon beta-1a counteracts effects of activation on the expression of G-protein-coupled receptor kinases 2 and 3, beta-arrestin-1, and regulators of G-protein signalling 2 and 16 in human mononuclear leukocytes

Cell Signal. 2002 Aug;14(8):673-8. doi: 10.1016/s0898-6568(02)00011-6.

Authors

Maurizio Giorelli¹, Paolo Livrea, Giovanni Defazio, Luisa Iacovelli, Loredana Capobianco, Antonietta Picascia, Michele Sallese, Davide Martino, Maria Stella Aniello, Maria Trojano, Antonio De Blasi

Affiliation

¹ Department of Neurologic and Psychiatric Sciences, University of Bari, I-70124 Bari, Italy. [email protected]

PMID: 12020767
DOI: 10.1016/s0898-6568(02)00011-6

Abstract

Activation regulates the responsiveness of G-protein-coupled receptors (GPCRs) on T cells, and modifications in the activity of GPCRs characterize lymphocytes from some immune disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Some lines of evidence suggest that such an effect is connected with the altered expression of some GPCRs regulatory proteins. Herein we demonstrate that phitoemagglutinin (PHA)-induced activation leads to differential expression of G-protein-coupled receptor kinase (GRK) 2, GRK3, beta-arrestin-1, regulators of G-protein signalling (RGS) 2, and RGS16 and decreases responsiveness of mononuclear leukocytes (MNL) to the beta-adrenergic agonist isoproterenol. Interferon beta-1a (IFN beta-1a), which is known to ameliorate the course of MS, counteracts the activation-induced effects on the expression of these GPCR regulatory proteins in MNL. Furthermore, IFN beta-1a quenches the effects of PHA on the isoproterenol-induced accumulation of cyclic AMP (cAMP). We suggest that regulation of GPCRs responsiveness may be a relevant property of IFN beta-1a in MS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic beta-Agonists / pharmacology
Arrestins / biosynthesis*
Arrestins / genetics
Cells, Cultured
Cyclic AMP / biosynthesis
Cyclic AMP-Dependent Protein Kinases / biosynthesis
Cyclic AMP-Dependent Protein Kinases / genetics
G-Protein-Coupled Receptor Kinase 3
Gene Expression Regulation
Humans
Interferon beta-1a
Interferon-beta / pharmacology*
Isoproterenol / pharmacology
Leukocytes, Mononuclear / metabolism*
Phytohemagglutinins / antagonists & inhibitors
Protein Biosynthesis
Protein Serine-Threonine Kinases / biosynthesis*
Protein Serine-Threonine Kinases / genetics
Proteins / genetics
RGS Proteins / biosynthesis*
RGS Proteins / genetics
RNA, Messenger / biosynthesis
Transcription, Genetic
beta-Adrenergic Receptor Kinases
beta-Arrestin 1
beta-Arrestins

Substances

ARRB1 protein, human
Adrenergic beta-Agonists
Arrb1 protein, mouse
Arrestins
Phytohemagglutinins
Proteins
RGS Proteins
RGS16 protein
RNA, Messenger
Rgs2 protein, mouse
beta-Arrestin 1
beta-Arrestins
Interferon-beta
Cyclic AMP
Protein Serine-Threonine Kinases
Cyclic AMP-Dependent Protein Kinases
G-Protein-Coupled Receptor Kinase 3
GRK3 protein, human
GRK3 protein, mouse
beta-Adrenergic Receptor Kinases
Isoproterenol
Interferon beta-1a