[Frontiers in Bioscience 13, 3637-3647, May 1, 2008]

The roles of chemokines in leukocyte recruitment and fibrosis in systemic sclerosis

Minoru Hasegawa1, Shinichi Sato2

1Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan, 2Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan

TABLE OF CONTENTS

1. Abstract
2. Pathogenesis of systemic sclerosis
3. The roles of immune cells
4. Mechanism of leukocyte recruitment
5. The roles of chemokines in tissue fibrosis
5.1. Chemokines
5.2. Monocyte chemoattractant protein 1/CCL2
5.3. Other CC chemokines
5.4. CXC chemokines
5.5. CX3C chemokines
5.6. Chemokines and fibrocytes
6. The roles of chemokines in vascular injury
7. Conclusions and perspective
8. Acknowledgements
9. Reference

1. ABSTRUCT

Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition and vascular injury in the skin and other visceral organs. Although the pathogenesis remains unclear, interactions among leukocytes, endothelial cells, and fibroblasts are likely to be central to the pathogenesis of the disease. Chemokines mediate the leukocyte chemotaxis and migration through endothelia into the organ tissues, leading to the interaction between leukocytes and fibroblasts. While amounts of literatures reported chemokine abnormalities in SSc, which might explain the altered accumulation of effector leukocyte subsets in the affected tissues. Among various chemokines, monocyte chemoattractant protein-1 (MCP-1/CCL2) likely has the most critical role for tissue fibrosis in SSc. Although therapeutic effect for targeting MCP-1 has been demonstrated in mouse models of SSc or fibrotic disorders, it is unknown whether this strategy is effective in human clinical trials. Here recent data will be reviewed on the pathogenic role of chemokines and their receptors in SSc.