Role of cytokines and proteases in murine scleroderma

Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not been fully elucidated, a growing body of evidence suggests that the overproduction of extracellular matrix proteins by activated fibroblasts results from an imbalance between synthesis and degradation of connective tissues. A number of mediators, cytokines, chemokines and growth factors secreted by inflammatory cells and mesenchymal cells (fibroblasts and myofibroblasts) play an important role in the fibrotic process of scleroderma. In this article, we describe recent advances concerning immunological aspects in the pathogenesis of bleomycin-induced murine scleroderma, laying stress on the involvement of interleukin-13 (IL-13) and plasminogen activator inhibitor-1 (PAI-1).