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Int J Mol Sci. 2015 Mar 11;16(3):5635-65. doi: 10.3390/ijms16035635.

Molecular mechanisms underlying β-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells.

Author information

1
College of Arts and Sciences, Kent State University, Kent, OH 44304, USA. ddifran7@kent.edu.
2
Department of Human Anatomy and Pathology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA. dbellinger@kent.edu.

Abstract

Cross-talk between the sympathetic nervous system (SNS) and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE) in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs) in immune cells activates the cAMP-protein kinase A (PKA) intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune-SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP-PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP-PKA to mitogen-activated protein kinase (MAPK) pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for "signal switching" in immune cells.

PMID:
25768345
PMCID:
PMC4394497
DOI:
10.3390/ijms16035635
[Indexed for MEDLINE]
Free PMC Article

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