Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

International Journal of Molecular Sciences

Dianne Lorton¹  Denise L. Bellinger² 

[1] College of Arts and Sciences, Kent State University, Kent, OH 44304, USA;Department of Human Anatomy and Pathology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA; E-Mail:

关键词: Neural–immune interactions;    stress;    β₂-adrenergic receptor signaling;    GRK;    β-arrestin;    PKA;    ERK1/2;    receptor regulation;    innate and adaptive immunity;   

DOI  :  10.3390/ijms16035635

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.