The role of leukotrienes in the pathogenesis of systemic sclerosis

Abstract

Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. SSc-related involvement of the lungs, heart, kidneys and/or the gastrointestinal system accounts for the increased mortality of scleroderma patients. Despite the progress which has recently been made in this field, the treatment of SSc is still unsatisfactory due to the low efficacy and/or high toxicity of available therapies. Leukotrienes are a family of lipid mediators synthesized from arachidonic acid in a process mediated by 5-lipoxygenase; they include leukotriene B4 and a group of cysteinyl leukotrienes: C4, D4, and E4. Leukotrienes play an important role in the regulation of all the processes vital to the pathogenesis of SSc, namely inflammation, vascular function and connective tissue remodeling. The available data suggests that an excessive synthesis of leukotrienes may contribute to the development and progression of SSc. Accordingly, blockade of leukotriene pathways appears to be a new, promising target for the treatment of

The Comparison of the Levels of Leukotriene B4, TGF-β1, Collagen in Keloid Fibroblasts and Normal Skin Fibroblast

“…In vitro research claims that the skin fibroblast of systemic sclerosis (SSc) of a patient contains more LTB4 compared to normal fibroblast. The expression of enzyme 5-LOX to the fibroblast culture of SSc patient's skin is higher compared to normal skin fibroblast [17].…”

“…Leukotriene B4 stimulates other proinflammatory cytokine synthesis including tumor necrosis factor alfa (TNFα), IL6, IL8 and fibroblas growth factor (FGF). The role of LTB4 in fibrosis is to stimulate fibroblast migration, induce collagen synthesis, differentiate fibroblast into mysfibroblast and stimulate epithel cells to synthesize TGF-β that plays a role in fibrosis process [17] [18]. In vitro research claims that the skin fibroblast of systemic sclerosis (SSc) of a patient contains more LTB4 compared to normal fibroblast.…”

“…Eicosanoide LTB4 can also be found in skin diseases such as atopic dermatitis and psoriasis and systemic sclerosis. In in vitro research of systemic sclerosis fibroblast, the level of LTB4 increased compared to healty skin fibroblast [17] [18]. The role of LTB4 in keloid phatogenesis particularly in inflammation phase and tissue proliferation in the process of wound recovery has not been thoroughly understood.…”

The association between vibration and vascular injury in rheumatic diseases: A review of the literature

“…These include platelet activation, impaired fibrinolysis, white blood cells (WBCs) activation, reduced red blood cells (RBCs) deformability and oxidative stress, increased viscosity, shear stress, and antiendothelial cell antibodies, all of which have been described in subsets of patients with RP [12,13,27,37]. Among them, platelet activation and shear stress were observed in VRP and SSc, and WBCs activation has been reported in patients with SSc, VRP and HAVS [12,27,38]. WBCs can physically obstruct the circulation by aggregating to each other and adhering to the vascular wall.…”

Rheumatic diseases during pregnancy

“…The rarity of the disease as well as its propensity to appear in the early 1940s, explain the low frequency of concurrent sclero-derma and pregnancy60. Leukotrienes play an important role in the regulation of all the processes vital to the pathogenesis of SSc namely inflammation, vascular function and connective tissue remodeling 61 . Many factors can lead to immunologic system disturbances and vascular changes.…”