Scleroderma

The increased expression of MCP-1 by SSc fibroblasts is thought to contribute to the presence of perivascular infiltrates of inflammatory cells in SSc patients, implicating a role in early processes leading to SSc lesions. This was supported in an experimental model of SSc, where MCP-1 was expressed before the development of any skin or lung […]

IL-6 IL-6 levels are elevated in serum from SSc patients and correlate positively with skin thickness, making it a useful serological indicator of skin fibrosis . IL-6 production by SSc fibroblasts is significantly increased (30-fold) compared with normal fibroblasts and may be the result of constitutive binding of nuclear factors to the IL-6 promoter. Treatment […]

Pentoxifylline (PTX) inhibited proliferation and collagen synthesis by cultured fibroblasts and myofibroblasts stimulated with PDGF and cultured SSc fibroblasts. It also prevented the development of liver fibrosis in an experimental model. A recent study revealed that PTX interrupts PDGF-driven fibropro-liferation by inhibiting PDGF-induced expression of c-jun . Antisense to c-jun also inhibited PDGF-induced fibroproliferation in […]

CTGF is a mitogen for endothelial cells and fibroblasts, that is induced by TGF-P and stimulates the production of ECM components including type I collagen . CTGF expression is significantly higher in skin fibroblasts, plasma and blister fluids from SSc patients compared with controls . Whereas TGF-P is detectable in certain prefibrotic lesions, CTGF is […]

Disease stage and duration are important factors in determining appropriate therapeutic targets, with immunomodulation as the early goal followed by prevention or reversal of fibrosis in later stages. Cytokines are important therapeutic targets because of their role in immune activation, fibroblast proliferation and extracellular matrix (ECM) accumulation in SSc. Key cytokines in SSc include transforming […]

Unfortunately, GI involvement often goes unnoticed until complications have already arisen and, thus, the general therapeutic approach is to treat SSc manifestations as they arise. There are no effective treatments targeting the underlying disease process but understanding the factors that contribute to SSc pathology will enable the development of new therapies for this elusive and […]

Systemic sclerosis (SSc), or scleroderma, is a connective tissue disorder characterized by progressive fibrosis of the skin and internal organs, as well as prominent changes in the microvasculature. There are two main subsets of the disease, referred to as limited and diffuse SSc. Diffuse SSc is the more serious form, because it affects visceral organs […]