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MR Vol.12 No.2 indexに戻る
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MODERN RHEUMATOLOGY
Vol.12 No.2 |
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Chemokines and chemokine receptors in the pathogenesis
of systemic sclerosis |
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| O. Distler1, J. Distler1, O. Kowal-Bielecka
, R. E. Gay1, U. Muller-Ladner3, S. Gay1 |
(1)WHO Collaborating Center for Molecular
Biology and Novel Therapeutic Strategies for Rheumatic Diseases,
University Hospital Zurich, CH-8091 Zurich, Switzerland
(2)Department of Rheumatology and Internal Medicine, Medical Academy of Bia^ystok,
Bia^ystok, Poland
(3)Department of Internal Medicine I, University of Regensburg, Regensburg,
Germany |
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| Abstract |
| Abstract Activation of the immune system and
increased synthesis of extracellular matrix proteins by fibroblasts
are hallmarks in the pathogenesis of systemic sclerosis (SSc).
The mechanisms that initiate the accumulation of inflammatory cells
are still unknown. Chemokines are a family of small molecules that
are divided into subfamilies according to the position of NH2-terminal
cysteine motif. A new nomenclature for chemokines recently has
been introduced in an attempt to overcome the confusion resulting
from a number of different names for the same chemokines. Recent
data indicate that chemokines, and in particular MCP-1 (CCL2),
might be involved in the pathogenesis of SSc at different levels.
MCP-1 is highly upregulated in skin specimens from SSc patients
compared with those from healthy controls. Dermal fibroblasts release
MCP-1, which is able to induce and perpetuate the migration of
inflammatory cells into the skin. Interestingly, data from animal
models, as well as from in vitro studies, indicate that MCP-1 might
also be involved in the increased synthesis of extracellular matrix
proteins, by either direct or indirect mechanisms. In conclusion,
chemokines represent interesting candidates for target-directed
therapies for SSc. This concept has to be confirmed by further
studies using animal models for SSc and other fibrotic diseases. |
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| Key words |
| Key words Chemokine receptors ・ Chemokines
・ Monocyte chemoattractant protein-1 (MCP-1) ・ Systemic sclerosis
(SSc) |
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