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Rheumatology Advance Access originally published online on November 4, 2008
Rheumatology 2009 48(2):98-103; doi:10.1093/rheumatology/ken401
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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Monocyte chemoattractant proteins in the pathogenesis of systemic sclerosis

J. H. W. Distler1, A. Akhmetshina1, G. Schett1 and O. Distler2

1Department of Rheumatology and Internal Medicine, University of Erlangen-Nuremberg, Erlangen, Germany and 2Center of Experimental Rheumatology and Zurich Center of Integrative Human Physiology, University Hospital Zurich, Zurich, Switzerland.

Correspondence to: J. H. W. Distler, Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, G1054 Erlangen, Germany. E-mail: joerg.distler{at}uk-erlangen.de


  Abstract

Activation of the immune system and increased synthesis of extracellular matrix proteins by fibroblasts are hallmarks in the pathogenesis of SSc. The molecular mechanisms underlying the infiltration of inflammatory cells into the skin and the subsequent activation of fibroblasts are still largely unknown. Chemokines are a family of small molecules that are classified according to the position of the NH2-terminal cysteine motif. Recent data indicate that chemokines and in particular two members of the subfamily of monocyte chemoattractant proteins, MCP-1 (CCL-2) and MCP-3 (CCL-7), might be involved in the pathogenesis of SSc. MCP-1 and -3 are overexpressed by SSc fibroblasts and in skin lesions from SSc patients compared to healthy controls. MCP-1 and -3 are chemotactic for inflammatory cells and stimulate their migration into the skin. In addition to their pro-inflammatory effects, MCP-1 and -3 contribute to tissue fibrosis by activating the synthesis of extracellular matrix proteins in SSc fibroblasts. Therapeutic strategies targeting MCP-1 have revealed promising results in several animal models of SSc. Antagonists against the receptor CCR2 are currently tested in clinical trials of a variety of diseases and also represent interesting candidates for target-directed therapy in SSc.

KEY WORDS: Chemokines, Chemokine receptors, Systemic sclerosis, MCP-1

Submitted 10 July 2008; revised version accepted 15 September 2008.
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