1,721,044 research outputs found
Shaping the gradient by nonchemotactic chemokine receptors
No full textChemokines are a class of inflammatory mediators which main function is to direct leukocyte migration through the binding to G protein-coupled receptors (GPCRs). In addition to these functional, signal-transducing chemokine receptors other types of receptors belonging to the chemokine GPCR family were identified. They are called atypical or decoy chemokine receptors because they bind and degrade chemokines but do not transduce signals or activate cell migration. Here there is the summary of two recent papers that identified other nonchemotactic chemokine receptors: the Duffy antigen receptor for chemokines (DARC) that mediates trancytosis of chemokines from tissue to vascular lumen promoting chemokine-mediated leukocyte transmigration and chemokine (CC motif) receptor-like 2 (CCRL2) that neither internalizes its ligands nor transduces signals but presents bound ligands to functional signaling receptors improving their activity. Collectively these nonchemotactic chemokine receptors do not directly induce cell migration, but appear nonetheless to play a nonredundant role in leukocyte recruitment by shaping the chemoattractant gradient, either by removing, transporting or concentrating their cognate ligands
Chemokines and their receptors : roles in specific clinical conditions and measurement in the clinical laboratory
No full textConsiderable progress has been achieved in our knowledge of the function of the chemokine system and in understanding its role in the pathophysiology of human diseases. This complex system, presently including approximately 50 cytokines and 20 receptors, coordinates leukocyte recruitment in a variety of human diseases, ranging from infectious and inflammatory diseases to cancer. A large body of literature has been published describing various assays for the measurement of chemokines in biologic fluids and tissues. We review information available on the role of chemokines in selected human diseases and provide examples of clinical situations in which chemokine determination might be of practical value, and we describe the currently available assays for their measurement
Chemokine regulation of neutrophil function in tumors
No full textThe role of neutrophils in cancer and metastasis is still debated and controversial since they have been shown to be endowed with both pro- and antitumor functions. These contradictory results seem to be now explained by recent discoveries of tumor-associated neutrophils plasticity and multiple neutrophil subsets. Chemokines and chemokine receptors are known to tightly regulate the release of neutrophils from the bone marrow, their passage into circulation and transmigration into the tissues as well as tumor infiltration. It is emerging that chemokine receptors are differentially expressed by neutrophil subsets and they affect not only their recruitment but also their effector functions. Here we are resuming human and murine data suggesting that therapeutic modulation of neutrophil activity through the targeting of specific chemokines or chemokine receptors can improve their anti-tumoral properties
Atypical chemokine receptors in cancer : Friends or foes?
No full textThe chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CCchemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXCchemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies
Targeting Chemokines in Cancer
No full textThe chemokine system is now recognized as a key element in cancer-related inflammation because it can affect tumor progression acting on tumor-stroma and also directly on tumor cells. Chemokines are produced by both tumor cells and the tumor microenvironment and modulate not only leukocyte infiltration and angiogenesis but also senescence, cell survival and metastasis. Here, we review available information in preclinical and clinical settings that suggest that the chemokine system represents a valuable target for the development of innovative therapeutic strategies
Chemoattractant receptors and leukocyte recruitment : more than cell migration
No full textChemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants but do not induce cell migration. These atypical “chemoattractant receptors” are unable to activate transduction events that lead directly to cell migration, but appear nonetheless to play a nonredundant role in leukocyte recruitment by shaping the chemoattractant gradient, either by removing, transporting, or concentrating their cognate ligands
Atypical chemokine receptors : from silence to sound
Full text linkACRs (atypical chemokine receptors) were initially referred to as 'silent' receptors on the basis of a lack of signalling and functional activities that are typically observed with conventional chemokine receptors. Although ACRs do not directly induce cell migration, they indirectly control leucocyte recruitment by shaping chemokine gradients in tissues through degradation, transcytosis or local concentration of their cognate ligands. Recent evidence also suggests that these biological activities are supported by G-protein-independent, beta-arrestin-dependent signalling events. In the present article, we review current knowledge on structural and signalling properties of ACRs that are changing our view on this entire class of receptors from silent to endogenous beta-arrestin-biased signalling receptors
Chemokines as pharmacological targets
No full textChemokines play a key role in immune processes by controlling leukocyte recruitment in physiological and pathological condition. This review discusses the regulation of the chemokine system, its role in human diseases, and its potential relevance as a new pharmacological target
Chemokine receptors intracellular trafficking
No full textChemokines coordinate leukocyte recruitment during inflammatory and immune responses through the interaction with a distinct subfamily of G protein-coupled receptors. The magnitude of the cellular response elicited by chemokines is dictated by the level of receptor expression at the plasma membrane, which is the balance of finely tuned endocytic and recycling pathways. Recent data have revealed that receptor trafficking properties can drive chemokine receptors to lysosomal degradation or recycling pathways, producing opposite effects on the strength of the intracellular signaling cascade. This review will cover recent advances on the molecular mechanisms underlying chemokine receptor internalization, recycling and degradation pathways, with particular attention to structural motifs present in receptor intracellular domains and their interacting adaptor proteins that modulate receptor trafficking and dictate proper biological response
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