title: 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.
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.
authors.affiliation: Department of Neurologic and Psychiatric Sciences, University of Bari, I-70124 Bari, Italy. m.giorelli@libero.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Giorelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Livrea
authors.forename: Giovanni
authors.initials: G
authors.lastname: Defazio
authors.forename: Luisa
authors.initials: L
authors.lastname: Iacovelli
authors.forename: Loredana
authors.initials: L
authors.lastname: Capobianco
authors.forename: Antonietta
authors.initials: A
authors.lastname: Picascia
authors.forename: Michele
authors.initials: M
authors.lastname: Sallese
authors.forename: Davide
authors.initials: D
authors.lastname: Martino
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Aniello
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Antonio
authors.initials: A
authors.lastname: De Blasi
mesh_terms: 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
chemical_list: 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