The Biology of Chemokines and their Receptors

Pharmingen Inc., San Diego, California 92121-1111, USA.
Annual Review of Immunology (Impact Factor: 41.39). 02/2000; 18(1):217-42. DOI: 10.1146/annurev.immunol.18.1.217
Source: PubMed

ABSTRACT During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection (1). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation (2), B (3), and T (4) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis (5). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines' biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.

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    • "The other CXC chemokine-2, CXCL2 has been shown to be associated with immune-regulatory and inflammatory processes [18]. Both CXCL1 and CXCL2 are ELR + CXC chemokine subtype [120] [122]. Both of these chemokines mediate their effects through binding to the receptor CXCR2 [19]. "
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    ABSTRACT: Recently, there has been growing attention to the role of the tumor microenvironment (TME) in cancer growth, metastasis and emergence of chemotherapy resistance. Stromal and tumor cells make up the TME and interact with each other through a complex cross-talk manner. This interaction is facilitated by a variety of growth factors, cytokines, chemokines and S100 proteins. In this review, we focus on chemokines and their cognate receptors in regulating the tumorigenic process. Chemokines are cytokines that have chemotactic potential. Chemokine receptors are expressed on tumor cells and stromal cells. Chemokines and their cognate receptors modulate tumor growth and metastasis in a paracrine and autocrine manner. They play a major role in the modulation of stromal cell recruitment, angiogenic potential, cancer cell proliferation, survival, adhesion, invasion and metastasis to distant sites. In addition, a new class of calcium binding family S100 proteins has getting attention as they play significant roles in tumor progression and metastasis by modulating TME. Here, we highlight recent developments regarding the inflammatory chemokine/S100 proteins systems in the TME. We also focus on how chemokines/S100 proteins, through their role in the TME, modulate cancer cell ability to grow, proliferate, invade and metastasize to different organs. This review highlights the possibility of using the chemokine/chemokine receptor axis as a promising strategy in cancer therapy, the current difficulties in achieving this goal, and how it could be overcome for successful future therapeutic intervention. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 05/2015; 365(1). DOI:10.1016/j.canlet.2015.05.002 · 5.62 Impact Factor
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    • "CCL19/MIP-3β /ELC 9p13.3 CCR7,11 MSC Macrophage chemotaxis during inflammation Rossi and Zlotnik 2000; Schinköthe et al. 2008 "
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    ABSTRACT: Chemokines secreted from different cellular components of bone marrow (BM) play an important role in the formation of the BM niche system. The hematopoietic stem cell (HSC) pool located in specialized anatomical sites within the BM is subjected to a complex network of chemokines, such that the produced chemokines affect the fate of these cells. Expression of different chemokine receptors on leukemic stem cells (LSCs) uncovers the critical role of chemokines in the maintenance, survival and fate of these cells in the leukemic niche. As a pre-metastatic niche rich in a variety of chemokines, the BM niche is turned into a locus of tumor cell development and division. The chemokine receptors expressed on the surface of metastatic cells lead to their metastasis and homing to the BM niche. Knowledge of chemokines and their receptors leads to the production of various therapeutic antagonists at chemokine receptors expressed on leukemic and tumor cells, enabling interference with chemokine function as a therapeutic tool. New findings suggest that miRNAs, with their specific inhibitory function, affect the ability of producing and expressing chemokines and chemokine receptors. This review focuses on the emerging role of chemokines and their receptors in normal and pathologic conditions of the BM niche, and also discusses the new therapeutic methods with this background.
    Cell and Tissue Research 02/2015; DOI:10.1007/s00441-015-2129-4 · 3.33 Impact Factor
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    • "In this work we have shown that CCL5 either delivered by a lentiviral vector or induced pharmacologically by chronic morphine inhibits the neurotoxic action of M-tropic gp120. CCL5 is a promiscuous ligand that binds to different receptors; however, the main receptor for CCL5 is CCR5 (Rossi and Zlotnik, 2000). In the adult brain, non-neuronal cells such as microglia, astrocytes and oligodendrocytes express this receptor (He et al., 1997; Klein et al., 1999; van der Meer et al., 2000). "
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    ABSTRACT: The human immunodeficiency virus (HIV) envelope protein gp120 promotes neuronal injury which is believed to cause HIV-associated neurocognitive disorders. Therefore, blocking the neurotoxic effect of gp120 may lead to alternative strategies to reduce the neurotoxic effect of HIV. In vitro, the neurotoxic effect of M-tropic gp120BaL is reduced by the chemokine CCL5, the natural ligand of CCR5 receptors. To determine whether CCL5 reduces the toxic effect of gp120BaL in vivo, animals were intrastriatally injected with lentiviral vectors overexpressing CCL5 prior to an intrastriatal injection of gp120BaL (400 ng). Neuronal injury was determined by silver staining, cleaved caspase-3 and TUNEL. Overexpression of CCL5 decreased gp120-mediated neuronal injury. CCL5 expression can be up-regulated by chronic morphine. Therefore, we examined whether morphine reduces the neurotoxic effect of gp120BaL. Rats stereotaxically injected with gp120BaL into the striatum received saline or chronic morphine for five days (10 mg/kg escalating to 30 mg/kg twice a day). Morphine-treated rats showed a decrease in all markers used to determine neuronal degeneration compared to saline-treated rats. The neuroprotective effect of morphine was significantly attenuated by expressing CCL5 shRNA. Our results suggest that compounds that increase the endogenous production of CCL5 may be used to reduce the pathogenesis of HIV-associated neurocognitive disorders. Copyright © 2015. Published by Elsevier Ltd.
    Neuropharmacology 01/2015; 92. DOI:10.1016/j.neuropharm.2015.01.009 · 4.82 Impact Factor
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