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Arthritis Rheum. 2007 Nov;56(11):3814-26.

The nuclear autoantigen CENP-B displays cytokine-like activities toward vascular smooth muscle cells.

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  • 1Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Québec, Canada.

Abstract

OBJECTIVE:

A growing number of intracellular autoantigenic polypeptides have been found to play a second biologic role when they are present in the extracellular medium. We undertook this study to determine whether the CENP-B nuclear autoantigen could be added to this set of bifunctional molecules.

METHODS:

Purified CENP-B or CENP-B released from apoptotic cells was tested for surface binding to a number of human cell types by cell-based enzyme-linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. The biologic effects of CENP-B on the migration, interleukin secretion, and signaling pathways of its specific target cells were evaluated.

RESULTS:

CENP-B was found to bind specifically to the surface of human pulmonary artery smooth muscle cells (SMCs) and not to fibroblasts or endothelial cells (ECs). Furthermore, CENP-B bound preferentially to SMCs of the contractile type rather than to SMCs of the synthetic type. Binding of CENP-B to SMCs stimulated their migration during in vitro wound healing assays, as well as their secretion of interleukins 6 and 8. The mechanism by which CENP-B mediated these effects involved the focal adhesion kinase, Src, ERK-1/2, and p38 MAPK pathways. Finally, CENP-B released from apoptotic ECs was found to bind to SMCs, thus indicating a plausible in vivo source of extracellular CENP-B.

CONCLUSION:

These novel biologic roles of the nuclear autoantigen CENP-B open up a new perspective for studying the pathogenic role of anti-CENP-B autoantibodies.

PMID:
17968937
DOI:
10.1002/art.22972
[PubMed - indexed for MEDLINE]
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