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.
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.
Giorelli
Maurizio
M
Department of Neurologic and Psychiatric Sciences, University of Bari, I-70124 Bari, Italy. m.giorelli@libero.it
Livrea
Paolo
P
Defazio
Giovanni
G
Iacovelli
Luisa
L
Capobianco
Loredana
L
Picascia
Antonietta
A
Sallese
Michele
M
Martino
Davide
D
Aniello
Maria Stella
MS
Trojano
Maria
M
De Blasi
Antonio
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D019390:Arrestins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D054770:G-Protein-Coupled Receptor Kinase 3; D005786:Gene Expression Regulation; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011506:Proteins / Q000235:genetics; D020710:RGS Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D051552:beta-Adrenergic Receptor Kinases; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
C000605253:ARRB1 protein, human; D000318:Adrenergic beta-Agonists; C000605255:Arrb1 protein, mouse; D019390:Arrestins; D010835:Phytohemagglutinins; D011506:Proteins; D020710:RGS Proteins; C107413:RGS16 protein; D012333:RNA, Messenger; C105345:Rgs2 protein, mouse; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D016899:Interferon-beta; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D054770:G-Protein-Coupled Receptor Kinase 3; C517848:GRK3 protein, human; C517850:GRK3 protein, mouse; D051552:beta-Adrenergic Receptor Kinases; D007545:Isoproterenol; D000068556:Interferon beta-1a