Receptor regulation in neuroendocrine-immune communication: current knowledge and future perspectives.
Immune cells express receptors for every hormone or neurotransmitter we know so far. The neuroendocrine system signals to the immune system via the release of hormones and neurotransmitters that regulate cellular activity via these receptors. Much attention has been focused on the effect of glucocorticoids and catecholamines on the immune system. Glucocorticoids communicate with immune cells via glucocorticoid receptors of which the activity itself changes during immune activation. Many neuroendocrine mediators are ligands for G-protein coupled receptors on immune cells. Cytokines, oxygen-radicals, and catecholamines can influence the responsiveness of G-protein coupled receptors via decreasing the intracellular level of so-called G-protein coupled receptor kinases, of which the subtype GRK2 is highly expressed in immune cells. Therefore, changes in only one kinase can modulate the sensitivity of many receptors. We describe here that sensitivity of neuroendocrine receptors on immune cells is constantly regulated by inflammatory processes or chronic stress, which implies that not only the activity of the neuroendocrine system determines communication but that the sensitivity of receptors is a major factor in determining the final immune response. Finally, consequences of alterations in GRK2 during (neuro)-inflammatory diseases are discussed.
Heijnen
Cobi J
CJ
Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands. c.heijnen@umcutrecht.nl
D000293:Adolescent; D002908:Chronic Disease; D054769:G-Protein-Coupled Receptor Kinase 2; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000276:immunology; D009452:Neuroendocrinology; D015213:Neuroimmunomodulation / Q000502:physiology*; D009490:Neurosecretory Systems / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D011598:Psychoneuroimmunology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000276:immunology; D051552:beta-Adrenergic Receptor Kinases / Q000276:immunology* / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D020794:Receptor Protein-Tyrosine Kinases; C496567:GRK2 protein, human; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2