TNF‐α and IL‐4 regulate expression of fractalkine (CX<sub>3</sub>CL1) as a membrane‐anchored proadhesive protein and soluble chemotactic peptide on human fibroblasts

Yoshikawa, Mamoru; Nakajima, Toshiharu; Matsumoto, Kenji; Okada, Naoko; Tsukidate, Toshiharu; Iida, Makoto; Otori, Nobuyoshi; Haruna, Shinichi; Moriyama, Hiroshi; Imai, Toshio; Saito, Hirohisa

doi:10.1016/s0014-5793(04)00132-2

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…In any event, they are a useful model to study cellular CX 3 CL1 distribution and traffic inasmuch as this chemokine is endogenously expressed by both endothelial and epithelial cells (4,9,14,42). To ensure that the observed trafficking of CX 3 CL1 was not an idiosyncratic feature of transfected ECV-304 cells, we further confirmed our findings in other cell types known to express CX 3 CL1, namely fibroblasts (43) and, especially, primary arterial endothelial cells (5,6,9,12,44). CX 3 CL1 is synthesized as a 50 -75-kDa precursor that is rapidly processed, presumably glycosylated, yielding the mature 100-kDa species (45).…”

Section: Discussionsupporting

confidence: 78%

Recycling of the Membrane-anchored Chemokine, CX3CL1

Liu

Kulasingam

Alexander

et al. 2005

Journal of Biological Chemistry

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CX 3 CL1 (fractalkine) plays an important role in inflammation by acting as both chemoattractant and as an adhesion molecule. As for other chemokines, expression of CX 3 CL1 is known to be regulated at the level of transcription and translation. The unique transmembrane structure of CX 3 CL1 raises the possibility of additional functional regulation by altering its abundance at the cell surface. This could be accomplished in principle by changes in traffic between subcellular compartments. To analyze this possibility we examined the subcellular distribution of CX 3 CL1 in human ECV-304 cells stably expressing untagged or green fluorescent proteintagged forms of the chemokine. CX 3 CL1 was present in two distinct compartments, diffusely on the plasma membrane and in a punctate juxtanuclear compartment. The latter shared some features with, yet was distinct from the conventional endocytic pathway and may represent a specialized recycling subcompartment. Accordingly, surface CX 3 CL1 was found to be in dynamic equilibrium with the juxtanuclear vesicular compartment. Intracellular CX 3 CL1 co-localized with the SNARE (soluble N-ethylmaleimide factor attachment protein receptor) proteins syntaxin-13 and VAMP-3. Cleavage of VAMP-3 by tetanus toxin or impairment of syntaxin-13 function by expression of a dominant-negative allele inhibited the ability of internalized CX 3 CL1 to traffic back to the plasma membrane. These data demonstrate the existence of a dynamic, SNARE-mediated recycling of CX 3 CL1 from the cell surface to and from an endomembrane storage compartment. The intracellular storage depot may serve as a source of the chemokine that could be rapidly mobilized by stimuli.

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Section: Discussionsupporting

confidence: 78%

Recycling of the Membrane-anchored Chemokine, CX3CL1

Liu

Kulasingam

Alexander

et al. 2005

Journal of Biological Chemistry

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“…Our observations gain support from a study by Yoshikawa et al, 33 who showed that tumor necrosis factor-␣-and interleukin-4 -stimulated fibroblasts facilitate the accumulation of monocytes at inflammation sites. In our preliminary studies in high-cholesterol-diet-fed, LDL-receptor-knockout mice, we found well-developed atherosclerosis and intense expression of CD68 throughout the thickness of the aorta, implying that monocyte/macrophage adhesion is present not just in the subintima but also in the adventitial region, where fibroblasts are present.…”

Section: Biologic Function Of Lox-1 In Cardiac Fibroblastssupporting

confidence: 87%

Adhesion Molecule Expression in Fibroblasts

Chen

Liu

et al. 2005

Hypertension

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Abstract-The endothelial lectinlike, oxidatively (ox-) modified LDL receptor LOX-1 is a critical player in the pathogenesis of atherosclerosis and myocardial ischemia. Ox-LDL binding of LOX-1 results in the expression of various adhesion molecules, which attract monocytes to endothelial cells, an initial step in atherogenesis. We wished to examine the role of the ox-LDL/LOX-1 signaling pathway in fibroblasts, which naturally express low levels of LOX-1. Rat cardiac fibroblasts were transfected with either cytomegalovirus ( wt -transfected cells. These data suggest that in cardiac fibroblasts, ox-LDL binds to LOX-1 and activates p38 MAPK, followed by the expression of ICAM-1, VCAM-1, and MMP-1. Thus, fibroblasts transform into an endothelial phenotype on transfection with CMV-LOX-1 wt and subsequent exposure to ox-LDL. This study provides a useful model system (plasmid-transfected fibroblasts) to study the molecular biology of LOX-1.

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“…15 CX 3 CL1 is expressed on the surface of endothelial cells, 17 epithelial cells, 17,18 DCs 19,20 and neurons 21 and is induced by pro-inflammatory cytokines, such as interleukin (IL)-1 and tumor necrosis factor-a. 22,23 The CX 3 CL1 receptor, CX 3 CR1, is capable of mediating both leukocyte migration and firm adhesion. CX 3 CR1 is expressed on a number of leukocytes, including monocytes, T-cell subsets and NK cells, 24,25 and CX 3 CR1 expression has been recently described in platelets.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

et al. 2014

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Circulating monocytes (Mos) may continuously repopulate macrophage (MAC) or dendritic cell (DC) populations to maintain homeostasis. MACs and DCs are specialized cells that play different and complementary immunological functions. Accordingly, they present distinct migratory properties. Specifically, whereas MACs largely remain in tissues, DCs are capable of migrating from peripheral tissues to lymphoid organs. The aim of this work was to analyze the expression of the fractalkine receptor (CX 3 CR1) during the monocytic differentiation process. Freshly isolated Mos express high levels of both CX 3 CR1 mRNA and protein. During the Mo differentiation process, CX 3 CR1 is downregulated in both DCs and MACs. However, MACs showed significantly higher CX 3 CR1 expression levels than did DC. We also observed an antagonistic CX 3 CR1 regulation by interferon (IFN)-c and interleukin (IL)-4 during MAC activation through the classical and alternative MAC pathways, respectively. IFN-c inhibited the loss of CX 3 CR1, but IL-4 induced it. Additionally, we demonstrated an association between CX 3 CR1 expression and apoptosis prevention by soluble fractalkine (sCX 3 CL1) in Mos, DCs and MACs. This is the first report demonstrating sequential and differential CX 3 CR1 modulation during Mo differentiation. Most importantly, we demonstrated a functional link between CX 3 CR1 expression and cell survival in the presence of sCX 3 CL1.

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TNF‐α and IL‐4 regulate expression of fractalkine (CX₃CL1) as a membrane‐anchored proadhesive protein and soluble chemotactic peptide on human fibroblasts

Cited by 23 publications

References 35 publications

Recycling of the Membrane-anchored Chemokine, CX3CL1

Recycling of the Membrane-anchored Chemokine, CX3CL1

Adhesion Molecule Expression in Fibroblasts

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

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TNF‐α and IL‐4 regulate expression of fractalkine (CX3CL1) as a membrane‐anchored proadhesive protein and soluble chemotactic peptide on human fibroblasts

Cited by 23 publications

References 35 publications

Recycling of the Membrane-anchored Chemokine, CX3CL1

Recycling of the Membrane-anchored Chemokine, CX3CL1

Adhesion Molecule Expression in Fibroblasts

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

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TNF‐α and IL‐4 regulate expression of fractalkine (CX₃CL1) as a membrane‐anchored proadhesive protein and soluble chemotactic peptide on human fibroblasts