Bimodal effect of humic acids on the LPS-induced TNF-alpha release from differentiated U937 cells.
Humic substances (HS) have been reported to possess anti-inflammatory as well as pro-inflammatory properties. The anti-inflammatory activity was demonstrated in the rat paw edema model and we found a preliminary explanation in the 5-lipoxygenase inhibitory effect of humic acids (HA). The pro-inflammatory activity is reflected by the production and release of pro-inflammatory cytokines in HA-treated neutrophilic granulocytes. With regard to the potential use of HA as antiviral and UV-protective agents it appears advisable to investigate the role of HS in the inflammation process in more detail. Hence we tested four different HS preparations - two naturally occurring HA from the Altteich peatland in Germany, one fulvic acid (FA) preparation from a Finnish spruce forest and a synthetic HA-like polymer (caffeic acid oxidation product, KOP) for their influence on the lipopolysaccharide (LPS)-induced TNF-alpha release in human U937 cells. In addition, the cytotoxicity of HS was determined. The results demonstrate a concentration-dependent bimodal effect of HA on the TNF-alpha release of differentiated LPS-stimulated U937 cells for both the natural black peat HA from the Altteich peatland and the HA-like polymer KOP. Low HA concentrations (10-80 microg/ml) enhanced the TNF-alpha release by up to threefold (pro-inflammatory activity), while HA concentrations >100 microg/ml reduced it about 10-fold (anti-inflammatory activity). FA failed to enhance TNF-alpha release, but reduced it at higher concentrations (>200 microg/ml) by the half. Brown water HA did not exert any significant effect on TNF-alpha release. No HS-stimulated TNF-alpha release was also observed in the absence of exogenously supplied LPS. This means that HS, unlike endotoxin, are no inflammation-causing agents for LPS-untreated cells. Differences in the effect of individual HS on TNF-alpha release are discussed in connection with the polyanionic character of HS, their molecular mass distribution and the hitherto imperfectly known chemical structure.
Junek
R
R
Department of Natural Sciences, Zittau/Görlitz University of Applied Sciences, D-02763 Zittau, Germany.
Morrow
R
R
Schoenherr
J I
JI
Schubert
R
R
Kallmeyer
R
R
Phull
S
S
Klöcking
R
R
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D001578:Benzopyrans / Q000009:adverse effects / Q000494:pharmacology*; D002109:Caffeic Acids / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006812:Humic Substances / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000633:toxicity; D010944:Plants; D012987:Soil; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells
D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D002109:Caffeic Acids; D006812:Humic Substances; D008070:Lipopolysaccharides; D012987:Soil; D014409:Tumor Necrosis Factor-alpha; C040048:caffeic acid; C005023:fulvic acid