Changes in the G-protein-coupled receptor desensitization machinery during relapsing-progressive experimental allergic encephalomyelitis.
G-protein-coupled receptors (GPCR) play an important role in inflammation. Their responsiveness is regulated by G-protein-coupled receptor kinases (GRKs) and beta-arrestins. We show here that induction of experimental autoimmune encephalomyelitis (EAE) by myelin oligodendrocyte glycoprotein (MOG) resulted in a profound decrease in GRK2 and GRK6 protein in splenocytes during all phases of disease. GRK2 mRNA was also lower during EAE, although the decrease in mRNA was less pronounced than the decrease in GRK2 protein. Interestingly, beta-arrestin protein expression was significantly increased. Downregulation of GRK2 was restricted to the spleen and mesenteric lymph nodes and was not observed in peritoneal macrophages. Furthermore, EAE did not induce alterations in GRK2 expression in heart, liver and pituitary.
Vroon
Anne
A
Laboratory for Psychoneuroimmunology, Department of Immunology, University Medical Center Utrecht, Room KC03.068.0, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Lombardi
Maria Stella
MS
Kavelaars
Annemieke
A
Heijnen
Cobi J
CJ
D000818:Animals; D019390:Arrestins / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism*; D054768:G-Protein-Coupled Receptor Kinases; D019204:GTP-Binding Proteins / Q000502:physiology*; D008198:Lymph Nodes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D013154:Spleen / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases; D000071557:beta-Arrestins
D019390:Arrestins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000071557:beta-Arrestins; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6; D019204:GTP-Binding Proteins