The influence of toll-like receptor (TLR-) agonists on lysozyme activity, TNF-alpha secretion and intercellular adhesion in THP-1 cells.

Monocytes play a major role in modulating inflammation and can be found as circulating blood cells or, after extravasation, as differentiated tissue specific macrophages. The activation of TLRs (Toll-like receptors) modulates their action and contributes considerably to the eradication of pathogens. Aim of this study was to investigate the influence of TLR-agonists on TNF-alpha secretion and lysozyme activity in a comparative assay. To explore the importance of differentiation the monocytic cell line THP-1 was pre-treated with PMA and IFNy. Stimulation of undifferentiated cells with various bacterial antigens had almost no effect on TNFalpha secretion and lysozyme activity but influenced adhesion molecule expression clearly. Differentiated THP-1 cells were much more sensitive to further stimulation with TLR-agonists yet revealed an opposing effect on lysozyme activity and TNF-alpha secretion. The results suggest a coordinated activation of intercellular adhesion molecule expression and cytokine secretion in the differentiation process from monocytes to macrophages.

The influence of harpagoside and harpagide on TNFα-secretion and cell adhesion molecule mRNA-expression in IFNγ/LPS-stimulated THP-1 cells.

Inflammation does not only lead to pain and functio laesa in the affected tissue but is also implicated in the onset and progression of cardiovascular diseases and cancer. Many medicinal plants show anti-inflammatory properties yet plant-constituents and their effect on molecular pathways involved in the attenuation of inflammation as well as cell migration are only poorly understood. Harpagophytum procumbens DC. ex MEISN. is a potent plant used as an immune modulator in traditional herbal medicine. Aim of this study was to investigate the influence of harpagoside and harpagide on TNFα-secretion in undifferentiated and differentiated THP-1 cells under inflammatory conditions as well as their implication in cellular migration into inflamed tissue. We found that both iridoids decrease TNFα-secretion in PMA-differentiated THP-1 cells whereas undifferentiated cells were poorly affected. Yet, in undifferentiated cells harpagoside and harpagide induced mRNA-expression of certain proteins involved in leukocyte transmigration. Especially TNFα and ICAM-1 mRNA-expression was positively affected after 3h and expression could be maintained on high levels even after 48h. L-selectin and PSGL-1 were strongly induced after 48h of stimulation. This ambiguous effect of harpagoside and harpagide highlights their immune modulatory function by facilitating cell migration into the inflamed tissue, whereby in consequence the anti-inflammatory activity of the resident macrophages was also found to be promoted.