Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation

Abstract

Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. In addition to their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best known central action is their ability to act as immuno-inflammatory mediators. Indeed, these proteins regulate leukocyte infiltration in the brain during inflammatory and infectious diseases. However, we and others recently demonstrated that they are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. The goal of this review is to highlight the role of chemokines in the control of neuroendocrine functions. First, we will focus on the expression of chemokines and their receptors in the CNS, with the main spotlight on the neuronal expression in the hypothalamo-pituitary system. Secondly, we will discuss the role -we can now suspect -of chemokines and their receptors in the regulation of neuroendocrine functions. In conclusion, we propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions.

Increased cytokine and chemokine gene expression in the CNS of mice during heat stroke recovery

“…While historically thought of as leukocyte recruitment signals, the demonstration of constitutive expression of chemokines and chemokine receptors on a variety of CNS cell types (microglia, astrocytes, oligodendrocytes, neurons, and brain microvasculature) suggests they may serve as potent modulators of neural function during homeostasis, homeostatic challenge, and neuroinflammation (8). Several of the neuroendocrine functions altered by HS, such as T c regulation, water balance, and feeding behavior have been found to be sensitive to manipulations of chemokine signaling (7). These findings, along with our demonstration of robust chemokine changes during hypothermia, suggest additional examination of the function of CNS chemokines in HS recovery is warranted and may provide novel therapeutic targets for investigation.…”

Neural Crest–Derived Stem Cells Migrate and Differentiate Into Cardiomyocytes After Myocardial Infarction

“…Once induced, the direct migration of cells expressing the appropriate chemokine receptors occurs along a chemical ligand gradient, whereby cells move more strongly toward the higher concentration of chemokines. 25 MCP-1 is a key chemokine in the regulation of migration and infiltration of monocyte/macrophages. 26 MCP-1 expression and function has also been implicated in the pathogenesis of cardiovascular diseases.…”

Chemical Interactions between Fibrosarcoma Cancer Cells and Sensory Neurons Contribute to Cancer Pain

“…Our data are the first to support a role for CCL2 in regulating gene expression in DRG neurons. CCR receptors are G-protein-coupled receptors that stimulate phosphoinositide-3 kinase (PI3 kinase) and extracellular receptor kinase (ERK) in other cell types (Werle et al, 2002;Callewaere et al, 2007). Upregulation of TRPV1 in DRG neurons is partially dependent on ERK and PI3 kinase (Bron et al, 2003), but little is known about the intracellular pathways that contribute to expression of the Ca 2ϩ channel subunit ␣2␦1 in neurons.…”