Honke, Nadine and Wiest, Clemens J. and Pongratz, Georg (2022) beta 2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic during Collagen-Induced Arthritis. BIOMEDICINES, 10 (8): 1950. ISSN , 2227-9059
Full text not available from this repository. (Request a copy)Abstract
The sympathetic nervous system (SNS) has either a pro-inflammatory or anti-inflammatory effect, depending on the stage of arthritis. In the past, treatment of arthritic B cells with a beta 2-adrenergic receptor (beta 2-ADR) agonist has been shown to attenuate arthritis. In this study, the expression and signaling of beta 2-ADR in B cells during collagen-induced arthritis (CIA) were investigated to provide an explanation of why only B cells from arthritic mice are able to improve CIA. Splenic B cells were isolated via magnetic-activated cell sorting (MACS). Adrenergic receptors on B cells and intracellular beta 2-ADR downstream molecules (G protein-coupled receptor kinase 2 (GRK-2), beta-Arrestin 2, p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB)) were analyzed at different time points in naive and arthritic B cells with and without stimulation of beta 2-ADR agonist terbutaline by flow cytometry. beta 2-ADR-expressing B cells increase during CIA without a change in receptor density. Moreover, we observed a profound downregulation of GRK-2 shortly after induction of arthritis and an increase in beta-Arrestin 2 only at late stage of arthritis. The second messengers studied (p38, ERK1/2 and CREB) followed a biphasic course, characterized by a reduction at onset and an increase in established arthritis. Stimulation of CIA B cells with the beta-ADR agonist terbutaline increased pp38 MAPK independent of the timepoint, while pERK1/2 and pCREB were enhanced only in the late phase of arthritis. The phosphorylation of p38 MAPK, ERK1/2 and CREB in the late phase of arthritis was associated with increased IL-10 produced by B10 cells. The change of beta 2-ADR expression and signaling during sustained inflammation might be an integral part of the switch from pro- to anti-inflammatory action of sympathetic mechanisms in late arthritis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYMPATHETIC-NERVOUS-SYSTEM; RHEUMATOID-ARTHRITIS; BETA-ARRESTINS; FLOW-CYTOMETRY; CATECHOLAMINERGIC CELLS; INTERLEUKIN-10 PROMOTER; ADJUVANT ARTHRITIS; SYNOVIAL TISSUE; IMMUNE-SYSTEM; T-CELLS; B cells; rheumatoid arthritis; IL-10; beta 2-adrenergic receptors; autoimmune disease; CIA mouse model; signaling pathway; p38; CREB |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Feb 2024 10:26 |
| Last Modified: | 14 Feb 2024 10:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57376 |
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