Adjuvant arthritis induces down-regulation of G protein-coupled receptor kinases in the immune system

G protein-coupled receptors (GPCR) play a crucial role in the regulation of the immune response by, e.g., chemokines, PGs, and beta (2)-adrenergic ago nists, The responsiveness of these GPCRs is turned off by the family of G p rotein-coupled receptor kinases (GRK1-6), These kinases act by phosphorylat ing the GPCR in an agonist-dependent manner, resulting in homologous desens itization of the receptor. Although GRKs are widely expressed throughout th e body, leukocytes express relatively high levels of GRKs, in particular GR K2, -3, and -6, We investigated whether in vivo the inflammatory disease ad juvant arthritis (AA) induces changes in GRK expression and function in the immune system. In addition, we analyzed whether the systemic effects of AA also involve changes in GRKs in nonimmune organs. At the peak of the infla mmatory process, we observed a profound downregulation of GRK2, -3, and -6 in splenocytes and mesenteric lymph node cells from AA rats. Interestingly, no changes in GRK were observed in thymocytes and in nonimmune organs such as heart and pituitary, During the remission phase of AA, GRK levels in sp leen and mesenteric lymph nodes are returning to baseline levels, The decre ase in GRK2 at the peak of AA is restricted to CD45RA(+) B cells and CD4(+) T cells, and was not observed in CD8(+) T cells. In conclusion, we demonst rate in this study, for the first time, that an inflammatory process in viv o induces a tissue-specific down-regulation of GRKs in the immune system.