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Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro

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Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro. / Burster, Timo; Beck, Alexander; Poeschel, Simone; Øren, Anita; Baechle, Daniel; Reich, Michael; Roetzschke, Olaf; Falk, Kirsten; Boehm, Bernhard O; Youssef, Sawsan; Kalbacher, Hubert; Overkleeft, Herman; Tolosa, Eva; Driessen, Christoph.

In: IMMUNOLOGY, Vol. 121, No. 1, 01.05.2007, p. 82-93.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Burster, T, Beck, A, Poeschel, S, Øren, A, Baechle, D, Reich, M, Roetzschke, O, Falk, K, Boehm, BO, Youssef, S, Kalbacher, H, Overkleeft, H, Tolosa, E & Driessen, C 2007, 'Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro', IMMUNOLOGY, vol. 121, no. 1, pp. 82-93. https://doi.org/10.1111/j.1365-2567.2007.02540.x

APA

Burster, T., Beck, A., Poeschel, S., Øren, A., Baechle, D., Reich, M., Roetzschke, O., Falk, K., Boehm, B. O., Youssef, S., Kalbacher, H., Overkleeft, H., Tolosa, E., & Driessen, C. (2007). Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro. IMMUNOLOGY, 121(1), 82-93. https://doi.org/10.1111/j.1365-2567.2007.02540.x

Vancouver

Burster T, Beck A, Poeschel S, Øren A, Baechle D, Reich M et al. Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro. IMMUNOLOGY. 2007 May 1;121(1):82-93. https://doi.org/10.1111/j.1365-2567.2007.02540.x

Bibtex

@article{d96e11d5576c4291b5060bd0a17cb86a,
title = "Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro",
abstract = "The serine protease cathepsin (Cat) G dominates the proteolytic processing of the multiple sclerosis (MS)-associated autoantigen myelin basic protein (MBP) in lysosomes from primary human B cells and dendritic cells. This is in contrast to B-lymphoblastoid cell lines, where the asparagine endopeptidase (AEP) is responsible for this task. We have analysed microglia-derived lysosomal proteases for their ability to process MBP in vitro. In lysosomes derived from primary murine microglia, CatD, CatS, AEP and CatG were involved in the processing of MBP. Interestingly, when microglia were treated with interferon-gamma to mimic a T helper type 1-biased cytokine milieu in MS, CatG was drastically down-regulated, in contrast to CatS, CatB, CatL, CatD or AEP. This resulted in significantly increased stability of MBP and a selective lack of CatG-derived proteolytic fragments; however, it did not affect the gross pattern of MBP processing. Inhibition of serine proteases eliminated the processing differences between lysosomal extracts from resting microglia compared to interferon-stimulated microglia. Thus, the cytokine environment modulates lysosomal proteases in microglia by a selective down-regulation of CatG, leading to decreased MBP-processing by microglia-derived lysosomal proteases in vitro.",
keywords = "Animals, Antigen Presentation, Autoantigens, Cathepsin G, Cathepsins, Down-Regulation, Interferon-gamma, Lysosomes, Mice, Mice, Inbred Strains, Microglia, Myelin Basic Protein, Phenylmethylsulfonyl Fluoride, Protease Inhibitors, Serine Endopeptidases",
author = "Timo Burster and Alexander Beck and Simone Poeschel and Anita {\O}ren and Daniel Baechle and Michael Reich and Olaf Roetzschke and Kirsten Falk and Boehm, {Bernhard O} and Sawsan Youssef and Hubert Kalbacher and Herman Overkleeft and Eva Tolosa and Christoph Driessen",
year = "2007",
month = may,
day = "1",
doi = "10.1111/j.1365-2567.2007.02540.x",
language = "English",
volume = "121",
pages = "82--93",
journal = "IMMUNOLOGY",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Interferon-gamma regulates cathepsin G activity in microglia-derived lysosomes and controls the proteolytic processing of myelin basic protein in vitro

AU - Burster, Timo

AU - Beck, Alexander

AU - Poeschel, Simone

AU - Øren, Anita

AU - Baechle, Daniel

AU - Reich, Michael

AU - Roetzschke, Olaf

AU - Falk, Kirsten

AU - Boehm, Bernhard O

AU - Youssef, Sawsan

AU - Kalbacher, Hubert

AU - Overkleeft, Herman

AU - Tolosa, Eva

AU - Driessen, Christoph

PY - 2007/5/1

Y1 - 2007/5/1

N2 - The serine protease cathepsin (Cat) G dominates the proteolytic processing of the multiple sclerosis (MS)-associated autoantigen myelin basic protein (MBP) in lysosomes from primary human B cells and dendritic cells. This is in contrast to B-lymphoblastoid cell lines, where the asparagine endopeptidase (AEP) is responsible for this task. We have analysed microglia-derived lysosomal proteases for their ability to process MBP in vitro. In lysosomes derived from primary murine microglia, CatD, CatS, AEP and CatG were involved in the processing of MBP. Interestingly, when microglia were treated with interferon-gamma to mimic a T helper type 1-biased cytokine milieu in MS, CatG was drastically down-regulated, in contrast to CatS, CatB, CatL, CatD or AEP. This resulted in significantly increased stability of MBP and a selective lack of CatG-derived proteolytic fragments; however, it did not affect the gross pattern of MBP processing. Inhibition of serine proteases eliminated the processing differences between lysosomal extracts from resting microglia compared to interferon-stimulated microglia. Thus, the cytokine environment modulates lysosomal proteases in microglia by a selective down-regulation of CatG, leading to decreased MBP-processing by microglia-derived lysosomal proteases in vitro.

AB - The serine protease cathepsin (Cat) G dominates the proteolytic processing of the multiple sclerosis (MS)-associated autoantigen myelin basic protein (MBP) in lysosomes from primary human B cells and dendritic cells. This is in contrast to B-lymphoblastoid cell lines, where the asparagine endopeptidase (AEP) is responsible for this task. We have analysed microglia-derived lysosomal proteases for their ability to process MBP in vitro. In lysosomes derived from primary murine microglia, CatD, CatS, AEP and CatG were involved in the processing of MBP. Interestingly, when microglia were treated with interferon-gamma to mimic a T helper type 1-biased cytokine milieu in MS, CatG was drastically down-regulated, in contrast to CatS, CatB, CatL, CatD or AEP. This resulted in significantly increased stability of MBP and a selective lack of CatG-derived proteolytic fragments; however, it did not affect the gross pattern of MBP processing. Inhibition of serine proteases eliminated the processing differences between lysosomal extracts from resting microglia compared to interferon-stimulated microglia. Thus, the cytokine environment modulates lysosomal proteases in microglia by a selective down-regulation of CatG, leading to decreased MBP-processing by microglia-derived lysosomal proteases in vitro.

KW - Animals

KW - Antigen Presentation

KW - Autoantigens

KW - Cathepsin G

KW - Cathepsins

KW - Down-Regulation

KW - Interferon-gamma

KW - Lysosomes

KW - Mice

KW - Mice, Inbred Strains

KW - Microglia

KW - Myelin Basic Protein

KW - Phenylmethylsulfonyl Fluoride

KW - Protease Inhibitors

KW - Serine Endopeptidases

U2 - 10.1111/j.1365-2567.2007.02540.x

DO - 10.1111/j.1365-2567.2007.02540.x

M3 - SCORING: Journal article

C2 - 17302735

VL - 121

SP - 82

EP - 93

JO - IMMUNOLOGY

JF - IMMUNOLOGY

SN - 0019-2805

IS - 1

ER -