Sulodexide Down-Regulates the Release of Cytokines, Chemokines, and Leukocyte Colony Stimulating Factors from Human Macrophages: Role of Glycosaminoglycans in Inflammatory Pathways of Chronic Venous Disease

Abstract

Chronic venous disease (CVeD) is a debilitating condition that affects millions of individuals worldwide. The condition can result in varicose veins, or advance to severe skin changes and venous ulceration. The fundamental basis for CVeD is inflammation within the venous circulation and that it is subjected to increased hydrostatic pressure resulting in increased ambulatory venous pressure. The inflammation involves leukocytes, in particular macrophages and monocytes, inflammatory modulators and chemokines, cytokine expression, growth factors, metalloproteinase (MMP) activity, and many regulatory pathways that perpetuate inflammation. Sulodexide (SDX) is a glycosaminoglycan with pro-fibrinolytic and anti-thrombotic properties. We have previously demonstrated that SDX inhibits the secretion of pro-zymogen MMP-9 from human leukocytes without displacing high molecular complexes of MMP-9. The anti-inflammatory properties of SDX on activated leukocytes have not been well established. We hypothesized that SDX will reduce the secretion of inflammatory mediators from lipopolysaccharide (LPS)-stimulated macrophages. Therefore, we evaluated the effects of SDX on LPS-stimulated macrophage secretion of various inflammatory and anti-inflammatory cytokines, chemokines, and colony stimulating factors. We used microplatebased multiplex immunoassays. LPS-stimulated macrophages in vitro caused a substantial increase of interleukins, tumor necrosis factor, interferon, chemokines and colony stimulating factors. The addition of SDX caused both a dose-dependent and dose-independent decrease in nearly all of the inflammatory cytokines, chemokines and colony stimulating factors. These findings suggest that SDX has a significant effect on the release of inflammatory mediators from macrophages, and may be useful in the treatment of early and advanced CVeD.

Matrix metalloproteinases in the wound microenvironment: therapeutic perspectives

“…8,9,[82][83][84][85] Some authors have postulated the complex indirect inhibitory influence of heparin and GAG-sulodexide on MMPs (revealed especially by low-molecular-weight heparin fraction). 12,82 However, there are also data suggesting direct inhibitory properties of dermatan sulfate fraction in sulodexide.…”

Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner

“…LNT is a β-D-glucan extracted from shiitake mushrooms (Lentinus edodes). A role for LNT in regulating the immune system has been implicated both in vivo and in vitro by several studies (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Moreover, LNT has antitumour (23), antioxidation (24) and DNA damage repair activities (12).…”

“…The secretion of these factors by the BM is inducible. As a common inducer, the strong inflammatory agent lipopolysaccharides (LPSs) activate BM macrophages through multiple signalling pathways, such as MAPK, NF-κB (13) and PI3K-AKT (14), thereby inducing the production of various inflammatory cytokines (13) and colony-stimulating factors (15). CSF receptors (CSFRs) are located on the surface of granulocyte-committed haematopoietic progenitor, neutrophils and endothelial cells (16).…”

The effect of sulodexide on placental mitochondria function in rats with experimental preeclampsia

“…Клинические исследования подтверждают доказательства того, что гликозаминогликаны играют существенную роль в восстановлении нормальной функции эндотелия [29]. Есть данные, что сулодексид снижает количество воспалительных цитокинов, хемокинов и колониестимулирующих факторов, улучшая функцию эндотелия [30].…”