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
Author(s):
Ferdinando Mannello, Daniela Ligi, Matteo
Canale and Joseph D. Raffetto Pages 173 - 185 ( 13 )
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.
Keywords:
Chronic venous disease, inflammation,
glycosaminoglycan, pro-inflammatory cytokines, chemokines, sulodexide, U-937
macrophage-like cell line.
Affiliation:
Department of Biomolecular Sciences, Section
of Clinical Biochemistry and Cell Biology, University “Carlo Bo”, Via O.
Ubaldini 7, Urbino (PU), Italy.
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