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Cytokine gene expression and production by human LPS-stimulated mononuclear cells are inhibited by sulfated heparin-like semi-synthetic derivatives.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2004 Sep; Vol. 2 (9), pp. 1657-62. - Publication Year :
- 2004
-
Abstract
- Background: The K5 polysaccharide obtained from Escherichia coli strain 010:K5:H4 is a polymer of the disaccharidic unit formed by D-glucuronic acid and N-acetylglucosamine. This structure is akin to N-acetylheparosan, the precursory polymer of heparin and of heparan sulfate. This structural affinity with N-acetylated heparin and with de-sulfated heparin makes the K5 polysaccharide extremely useful for the preparation of sulfated heparin-like semi-synthetic derivatives. It has been demonstrated that heparins are able to inhibit tissue factor and cytokine production and expression by human monocytes.<br />Objective: The aim of this study was to evaluate the effects of four different heparin-like semi-synthetic derivatives on inflammatory cytokine production and expression by human mononuclear cells.<br />Results: The simultaneous addition of lipopolysaccharide (LPS; 0.2 and 10 micro g mL(-1)) and the K5 polysaccharide did not inhibit interleukin (IL)-1beta, IL-6 or tumor necrosis factor (TNF)-alpha production by stimulated mononuclear cells. IL-1beta, IL-6 and TNF-alpha concentrations in supernatants of LPS-stimulated mononuclear cells were not influenced by the addition of N,O-sulfated K5 polysaccharide (K5-N, OS) and epimerized N-sulfated K5 polysaccharide (K5 NS epi) at 5 and 10 microg mL(-1), whereas the addition of epimerized N,O-sulfated K5 polysaccharide (K5-N, OS epi) (5 and 10 microg mL(-1)) and O-sulfated K5 polysaccharide (K5-OS) (5 and 10 microg mL(-1)) to LPS-stimulated cells caused a significant dose-dependent inhibition of IL-1beta, IL-6 and TNF-alpha. All sulfated heparin-like semi-synthetic derivatives did not influence the IL-10 production by LPS-stimulated mononuclear cells. In LPS-stimulated cells (0.2 and 10 microg mL(-1)), K5-OS or K5-N, OS epi at 5 and 10 microg mL(-1) markedly decreased TNF-alpha mRNA expression.<br />Conclusions: These results indicate that the sulfated heparin-like semi-synthetic derivatives K5-OS and K5-N, OS epi are able to inhibit both expression and production of inflammatory cytokines, whereas they do not influence the anti-inflammatory cytokine IL-10, suggesting a potential role for these products as modulators of inflammatory reactions.
- Subjects :
- Bacterial Capsules
Gene Expression drug effects
Heparin chemical synthesis
Heparin pharmacology
Humans
In Vitro Techniques
Interleukin-1 biosynthesis
Interleukin-1 genetics
Interleukin-10 biosynthesis
Interleukin-10 genetics
Interleukin-6 biosynthesis
Interleukin-6 genetics
Lipopolysaccharides pharmacology
Polysaccharides, Bacterial pharmacology
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha genetics
Cytokines biosynthesis
Cytokines genetics
Heparin analogs & derivatives
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7933
- Volume :
- 2
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 15333044
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2004.00866.x