Altered Sympathetic-to-Immune Cell Signaling via β2-Adrenergic Receptors in Adjuvant Arthritis
| Autor: | Dianne Lorton, Denise L. Bellinger, Jill A. Schaller, Eric Shewmaker, Tracy Osredkar, Cheri Lubahn |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Clinical and Developmental Immunology, Vol 2013 (2013) |
| Druh dokumentu: | article |
| ISSN: | 1740-2522 1740-2530 |
| DOI: | 10.1155/2013/764395 |
| Popis: | Adjuvant-induced arthritic (AA) differentially affects norepinephrine concentrations in immune organs, and in vivo β-adrenergic receptor (β-AR) agonist treatment distinctly regulates ex vivo cytokine profiles in different immune organs. We examined the contribution of altered β-AR functioning in AA to understand these disparate findings. Twenty-one or 28 days after disease induction, we examined β2-AR expression in spleen and draining lymph nodes (DLNs) for the arthritic limbs using radioligand binding and western blots and splenocyte β-AR-stimulated cAMP production using enzyme-linked immunoassay (EIA). During severe disease, β-AR agonists failed to induce splenocyte cAMP production, and β-AR affinity and density declined, indicating receptor desensitization and downregulation. Splenocyte β2-AR phosphorylation (pβ2-AR) by protein kinase A (pβ2-ARPKA) decreased in severe disease, and pβ2-AR by G protein-coupled receptor kinases (pβ2-ARGRK) increased in chronic disease. Conversely, in DLN cells, pβ2-ARPKA rose during severe disease, but fell during chronic disease, and pβ2-ARGRK increased during both disease stages. A similar pβ2-AR pattern in DLN cells with the mycobacterial cell wall component of complete Freund’s adjuvant suggests that pattern recognition receptors (i.e., toll-like receptors) are important for DLN pβ2-AR patterns. Collectively, our findings indicate lymphoid organ- and disease stage-specific sympathetic dysregulation, possibly explaining immune compartment-specific differences in β2-AR-mediated regulation of cytokine production in AA and rheumatoid arthritis. |
| Databáze: | Directory of Open Access Journals |
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