Production and neuroprotective functions of fractalkine in the central nervous system

Mizuno, Tetsuya; Koyama, Jun; Numata, Kenji; Suzumura, Akio

doi:10.1016/s0006-8993(03)02867-1

Cited by 297 publications

(249 citation statements)

References 22 publications

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“…It is proposed that microglia has a prominent role in mediating the neuroprotective effects of CX3CL1 (Mizuno et al, 2003;Huang et al, 2006;Cardona et al, 2006) and we have recently shown that CX3CL1-stimulated microglia releases neuroprotective substances that reduce Glu-induced cell death (Lauro et al, 2008). However CX3CL1 does not protect against all types of neuronal damage because in transient brain ischemia (Soriano et al, 2002;Dénes et al, 2008) and in a rat model of Parkinson's disease, intrastriatal CX3CL1 injection induced both microglia-dependent depletion of dopaminergic cells and motor dysfunction (Shan et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…CX3CL1 is constitutively expressed in the nervous system, but levels in the brain can be modulated under diverse pathological conditions (Pan et al, 1997;Hughes et al, 2002;Kastenbauer et al, 2003;Sunnemark et al, 2005;Huang et al, 2006). The presence and the stimulation (Zujovic et al, 2000(Zujovic et al, , 2001Mizuno et al, 2003;Cardona et al, 2006;Lyons et al, 2009) of the CX3CL1 receptor CX3CR1 has been correlated with a reduced release of interleukin-1-b (IL-1-b) and tumor necrosis factor-a (TNF-a) from microglial cells and a lower rate of neuronal degeneration in different experimental models of neuropathologies such as experimental autoimmune encephalomyelitis, 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride striatal injection, lipopolysaccharide administration, and superoxide dismutase (SOD1) mutation (Huang et al, 2006;Cardona et al, 2006). These data attest to a role of the pair CX3CL1/CX3CR1 in reducing neuronal degeneration on several types of brain injury.…”

Section: Introductionmentioning

confidence: 99%

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Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Lauro

Cipriani

Catalano

et al. 2010

Neuropsychopharmacol

110

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Fractalkine/CX3CL1 is a neuron-associated chemokine, which modulates microglia-induced neurotoxicity activating the specific and unique receptor CX3CR1. CX3CL1/CX3CR1 interaction modulates the release of cytokines from microglia, reducing the level of tumor necrosis factor-a, interleukin-1-b, and nitric oxide and induces the production of neurotrophic substances, both in vivo and in vitro. We have recently shown that blocking adenosine A 1 receptors (A 1 R) with the specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) abolishes CX3CL1-mediated rescue of neuronal excitotoxic death and that CX3CL1 induces the release of adenosine from microglia. In this study, we show that the presence of extracellular adenosine is mandatory for the neurotrophic effect of CX3CL1 as reducing adenosine levels in hippocampal cultures, by adenosine deaminase treatment, strongly impairs CX3CL1-mediated neuroprotection. Furthermore, we confirm the predominant role of microglia in mediating the neuronal effects of CX3CL1, because the selective depletion of microglia from hippocampal cultures treated with clodronate-filled liposomes causes the complete loss of effect of CX3CL1. We also show that hippocampal neurons obtained from A 1 R À/À mice are not protected by CX3CL1 whereas A 2A R À/À neurons are. The requirement of functional A 1 R for neuroprotection is not unique for CX3CL1 as A 1 R À/À hippocampal neurons are not rescued from Glu-induced cell death by other neurotrophins such as brain-derived neurotrophic factor and erythropoietin, which are fully active on wt neurons.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Lauro

Cipriani

Catalano

et al. 2010

Neuropsychopharmacol

110

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“…83 In addition to increasing phagocytosis, FKN has also been associated with anti-inflammatory actions such as providing neuroprotection during glutamate toxicity, 84,85 modulating TNF-α secretion by microglia, 86 and promoting proliferative effects, 87,88 which may all have important roles in different settings of cell clearance. However, clarification is needed as to which processed form is responsible for these FKN effects.…”

Section: Steps Involved In Clearancementioning

confidence: 99%

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

2016

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The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of 'find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment.

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“…The physiological relevance of membrane and soluble FKN is not known; however, it is currently thought that membrane-associated FKN (m-FKN) predominantly mediates cell adhesion, whereas the soluble protein FKN (s-FKN) acts as a chemoattractant (22,30). The unique receptor for FKN, CX 3 CR1, is expressed on monocytes (3), subsets of T lymphocytes (24,45), mast cells (48), natural killer cells (33), dendritic cells (16), platelets (52), neurons, astrocytes, and microglial cells (31,40,42) and mediates both the adhesive and chemotactic functions of FKN.…”

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confidence: 99%

Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

Sukkar

Issa

Xie

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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mokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX 3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX3CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1␤, TNF-␣, and IFN-␥, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-␤. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-␥ and TNF-␣ induced FKN mRNA and protein expression in a time-and concentration-dependent manner. TGF-␤ had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10 Ϫ8 -10 Ϫ6 M) significantly upregulated cytokineinduced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 M) and SB-203580 (20 M), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-␥-and TNF-␣-induced JNK phosphorylation remained unaltered in the presence of TGF-␤ but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-␤-or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors. chemokine; airway inflammation; asthma; chronic obstructive pulmonary disease THERE IS NOW SUBSTANTIAL EVIDENCE suggesting that airway smooth muscle cells (ASMC), by virtue of their immunomodulatory functions, may be involved in regulating airway inflammatory responses in diseases such as asthma and chronic obstructive pulmonary disease (COPD). ASMC express adhesion molecules and synthesize many cytokines and chemokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, eotaxin, and RANTES. These mediators are critically implicated in the recruitment, survival, and activation of key effector cells, such as eosinophils, neutrophils, and T lymphocytes, in asthma and COPD (10).Fractalkine (FKN), also known as CX 3 C ligand 1 (CX 3 CL1), is a novel chemokine belonging to the CX 3 C chemokine family. FKN is a multidomain molecule expressed on the cell surface and consists of a transmembrane region and a heavily glycosylated mucin-like stalk that extends from the cell surface, holding the chemokine domain at its tip (5). FKN also exists as a soluble glycoprotein that is generated by proteolytic cleavage of the full-length molecule at a membrane-proximal site (27,32,55). The physiological relevance of membrane and soluble FKN is not known; however, it is cu...

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Production and neuroprotective functions of fractalkine in the central nervous system

Cited by 297 publications

References 22 publications

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

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Production and neuroprotective functions of fractalkine in the central nervous system

Cited by 297 publications

References 22 publications

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

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Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids