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The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10

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The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. / Abel, Soeren; Hundhausen, Christian; Mentlein, Rolf; Schulte, Alexander; Berkhout, Theo A; Broadway, Neil; Hartmann, Dieter; Sedlacek, Radek; Dietrich, Sebastian; Muetze, Barbara; Schuster, Bjoern; Kallen, Karl-Josef; Saftig, Paul; Rose-John, Stefan; Ludwig, Andreas.

in: J IMMUNOL, Jahrgang 172, Nr. 10, 15.05.2004, S. 6362-72.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Abel, S, Hundhausen, C, Mentlein, R, Schulte, A, Berkhout, TA, Broadway, N, Hartmann, D, Sedlacek, R, Dietrich, S, Muetze, B, Schuster, B, Kallen, K-J, Saftig, P, Rose-John, S & Ludwig, A 2004, 'The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10', J IMMUNOL, Jg. 172, Nr. 10, S. 6362-72.

APA

Abel, S., Hundhausen, C., Mentlein, R., Schulte, A., Berkhout, T. A., Broadway, N., Hartmann, D., Sedlacek, R., Dietrich, S., Muetze, B., Schuster, B., Kallen, K-J., Saftig, P., Rose-John, S., & Ludwig, A. (2004). The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J IMMUNOL, 172(10), 6362-72.

Vancouver

Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N et al. The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J IMMUNOL. 2004 Mai 15;172(10):6362-72.

Bibtex

@article{47cbb12021c945d4b6823cf75cc21ac1,
title = "The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10",
abstract = "The novel CXC-chemokine ligand 16 (CXCL16) functions as transmembrane adhesion molecule on the surface of APCs and as a soluble chemoattractant for activated T cells. In this study, we elucidate the mechanism responsible for the conversion of the transmembrane molecule into a soluble chemokine and provide evidence for the expression and shedding of CXCL16 by fibroblasts and vascular cells. By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule. Inhibition experiments with selective hydroxamate inhibitors against the disintegrin-like metalloproteinases a disintegrin and metalloproteinase domain (ADAM)10 and ADAM17 suggest that ADAM10, but not ADAM17, is involved in constitutive CXCL16 cleavage. In addition, the constitutive cleavage of transfected human CXCL16 was markedly reduced in embryonic fibroblasts generated from ADAM10-deficient mice. By induction of murine CXCL16 in ADAM10-deficient fibroblasts with IFN-gamma and TNF-alpha, we show that endogenous ADAM10 is indeed involved in the release of endogenous CXCL16. Finally, the shedding of endogenous CXCL16 could be reconstituted by retransfection of ADAM10-deficient cells with ADAM10. Analyzing the expression and release of CXCXL16 by cultured vascular cells, we found that IFN-gamma and TNF-alpha synergize to induce CXCL16 mRNA. The constitutive shedding of CXCL16 from the endothelial cell surface is blocked by inhibitors of ADAM10 and is independent of additional inhibition of ADAM17. Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue.",
keywords = "ADAM Proteins, Amyloid Precursor Protein Secretases, Animals, COS Cells, Cell Line, Tumor, Cell Membrane, Cells, Cultured, Chemokine CXCL6, Chemokines, CXC, Cytokines, Disintegrins, Endopeptidases, Endothelium, Vascular, Humans, Hydrolysis, Interferon-gamma, Membrane Proteins, Metalloendopeptidases, Mice, Mice, Knockout, Muscle, Smooth, Vascular, Protein Precursors, Protein Structure, Tertiary, Receptors, Immunologic, Receptors, Scavenger, Solubility, Tetradecanoylphorbol Acetate, Tumor Necrosis Factor-alpha",
author = "Soeren Abel and Christian Hundhausen and Rolf Mentlein and Alexander Schulte and Berkhout, {Theo A} and Neil Broadway and Dieter Hartmann and Radek Sedlacek and Sebastian Dietrich and Barbara Muetze and Bjoern Schuster and Karl-Josef Kallen and Paul Saftig and Stefan Rose-John and Andreas Ludwig",
year = "2004",
month = may,
day = "15",
language = "English",
volume = "172",
pages = "6362--72",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

RIS

TY - JOUR

T1 - The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10

AU - Abel, Soeren

AU - Hundhausen, Christian

AU - Mentlein, Rolf

AU - Schulte, Alexander

AU - Berkhout, Theo A

AU - Broadway, Neil

AU - Hartmann, Dieter

AU - Sedlacek, Radek

AU - Dietrich, Sebastian

AU - Muetze, Barbara

AU - Schuster, Bjoern

AU - Kallen, Karl-Josef

AU - Saftig, Paul

AU - Rose-John, Stefan

AU - Ludwig, Andreas

PY - 2004/5/15

Y1 - 2004/5/15

N2 - The novel CXC-chemokine ligand 16 (CXCL16) functions as transmembrane adhesion molecule on the surface of APCs and as a soluble chemoattractant for activated T cells. In this study, we elucidate the mechanism responsible for the conversion of the transmembrane molecule into a soluble chemokine and provide evidence for the expression and shedding of CXCL16 by fibroblasts and vascular cells. By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule. Inhibition experiments with selective hydroxamate inhibitors against the disintegrin-like metalloproteinases a disintegrin and metalloproteinase domain (ADAM)10 and ADAM17 suggest that ADAM10, but not ADAM17, is involved in constitutive CXCL16 cleavage. In addition, the constitutive cleavage of transfected human CXCL16 was markedly reduced in embryonic fibroblasts generated from ADAM10-deficient mice. By induction of murine CXCL16 in ADAM10-deficient fibroblasts with IFN-gamma and TNF-alpha, we show that endogenous ADAM10 is indeed involved in the release of endogenous CXCL16. Finally, the shedding of endogenous CXCL16 could be reconstituted by retransfection of ADAM10-deficient cells with ADAM10. Analyzing the expression and release of CXCXL16 by cultured vascular cells, we found that IFN-gamma and TNF-alpha synergize to induce CXCL16 mRNA. The constitutive shedding of CXCL16 from the endothelial cell surface is blocked by inhibitors of ADAM10 and is independent of additional inhibition of ADAM17. Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue.

AB - The novel CXC-chemokine ligand 16 (CXCL16) functions as transmembrane adhesion molecule on the surface of APCs and as a soluble chemoattractant for activated T cells. In this study, we elucidate the mechanism responsible for the conversion of the transmembrane molecule into a soluble chemokine and provide evidence for the expression and shedding of CXCL16 by fibroblasts and vascular cells. By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule. Inhibition experiments with selective hydroxamate inhibitors against the disintegrin-like metalloproteinases a disintegrin and metalloproteinase domain (ADAM)10 and ADAM17 suggest that ADAM10, but not ADAM17, is involved in constitutive CXCL16 cleavage. In addition, the constitutive cleavage of transfected human CXCL16 was markedly reduced in embryonic fibroblasts generated from ADAM10-deficient mice. By induction of murine CXCL16 in ADAM10-deficient fibroblasts with IFN-gamma and TNF-alpha, we show that endogenous ADAM10 is indeed involved in the release of endogenous CXCL16. Finally, the shedding of endogenous CXCL16 could be reconstituted by retransfection of ADAM10-deficient cells with ADAM10. Analyzing the expression and release of CXCXL16 by cultured vascular cells, we found that IFN-gamma and TNF-alpha synergize to induce CXCL16 mRNA. The constitutive shedding of CXCL16 from the endothelial cell surface is blocked by inhibitors of ADAM10 and is independent of additional inhibition of ADAM17. Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue.

KW - ADAM Proteins

KW - Amyloid Precursor Protein Secretases

KW - Animals

KW - COS Cells

KW - Cell Line, Tumor

KW - Cell Membrane

KW - Cells, Cultured

KW - Chemokine CXCL6

KW - Chemokines, CXC

KW - Cytokines

KW - Disintegrins

KW - Endopeptidases

KW - Endothelium, Vascular

KW - Humans

KW - Hydrolysis

KW - Interferon-gamma

KW - Membrane Proteins

KW - Metalloendopeptidases

KW - Mice

KW - Mice, Knockout

KW - Muscle, Smooth, Vascular

KW - Protein Precursors

KW - Protein Structure, Tertiary

KW - Receptors, Immunologic

KW - Receptors, Scavenger

KW - Solubility

KW - Tetradecanoylphorbol Acetate

KW - Tumor Necrosis Factor-alpha

M3 - SCORING: Journal article

C2 - 15128827

VL - 172

SP - 6362

EP - 6372

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 10

ER -